Golgi protein 73 and its diagnostic value in liver diseases

Yanyan Xia; Yuanying Zhang; Mengjiao Shen; Hongpan Xu; Zhiyang Li; Nongyue He

doi:10.1111/cpr.12538

. 2018 Oct 19;52(2):e12538. doi: 10.1111/cpr.12538

Golgi protein 73 and its diagnostic value in liver diseases

Yanyan Xia ¹, Yuanying Zhang ², Mengjiao Shen ¹, Hongpan Xu ¹, Zhiyang Li ^3,^✉, Nongyue He ^4,^✉

PMCID: PMC6496820 PMID: 30341783

Abstract

Golgi protein 73 (GP73, also referred to as Golph 2) with 400 amino acids is a 73 kDa transmembrane glycoprotein typically found in the cis‐Golg complex. It is primarily expressed in epithelial cells, which has been found upregulated in hepatocytes in patients suffering from both viral and non‐viral liver diseases. GP73 has drawn increasing attention for its potential application in the diagnosis of liver diseases such as hepatitis, liver cirrhosis and liver cancer. Herein, we reviewed the discovery history of GP73 and summarized studies by many groups around the world, aiming at understanding its structure, expression, function, detection methods and the relationship between GP73 and liver diseases in various settings.

Keywords: GP73, hepatitis, liver cancer, liver cirrhosis

1. INTRODUCTION

Golgi protein 73 (GP73) is a transmembrane protein that has been found on the Golgi apparatus in recent years. It is also known as Golgi membrane protein I or Golgi phosphor protein 2. Because its relative molecular mass in polyacrylamide gel electrophoresis is 7.3 × 10⁴, it is also called GP73.1, 2, 3, 4, 5, 6, 7, 8 At present, many studies have found that the GP73 protein is associated with liver diseases, especially with liver cancer diseases5, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23; therefore, it is expected to become a new serological tumour marker for early diagnosis of liver cancer, which has attracted widespread attention from research scholars.

The Golgi apparatus is mainly involved in protein secretion, glycosylation and membrane transformation. The maintenance of cellular spatial structure and execution of its functions is closely related to the Golgi's membrane‐resident protein.20, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 The Golgi apparatus can participate in signal transmission and cell differentiation and can also play an important role in cell apoptosis. Therefore, some functions of Golgi apparatus are abnormal, in particular, abnormal function of certain membrane proteins are most likely related to the occurrence and development of tumours.44, 45, 46, 47, 48, 49, 50, 51, 52

2. BASIC OVERVIEW OF GP73

2.1. The discovery of GP73

American scholar Kladney et al performed subtractive hybridization in liver cDNA libraries of healthy individuals and patients with acute adult giant cell hepatitis in 2000 and found that the mRNA expression in patients with adult giant cell hepatitis was specifically increased.53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 The mRNA encodes a protein GP73 containing 401 amino acids, and its relative molecular mass is 4.5 × 10⁴.64, 65, 66, 67, 68, 69, 70, 71 However, due to acidic amino acid effect and glycosylation of GP73, denaturation of GP73 protein was affected, and electrophoretic migration rate was decreased. The relative molecular mass of GP73 in the polyacrylamide gel electrophoresis was slightly larger, GP73 band abnormally migrated in the Western blot, and its relative molecular mass was 7.3 × 10⁴.72, 73, 74, 75, 76, 77, 78, 79

2.2. Structural features of GP73

The GP73 gene is located in the short arm of chromosome 9 at position 9q21.33. It has a total length of 3042 bp, containing 9 introns and 10 exons. It also contains a unique open‐reading frame (1200‐1430 bp) that encodes 400 amino acids.80, 81, 82, 83, 84 The 3′ untranslated region of GP73 gene contains three polyadenylation sites (3003, 2950 and 1448 bp) and a stop codon (bp 1351). The encoded protein contains more acidic amino acids, such as aspartic acid and glutamic acid, and the isoelectric point for the amino acid is 4.72, containing single transmembrane region and signal peptidase cleavage site aa28‐aa29 and N‐terminal hydrophobic (Figure 1).85, 86, 87, 88, 89, 90, 91, 92, 93 The amino acid encoded by C‐terminus is located in the extracellular region and contains 5 glycosylation sites and 14 cellulose acylated sequences.94, 95, 96 Several coiled coils immediately after the transmembrane region can participate in the interaction between proteins, and their characteristics indicate that the GP73 protein can interact with other proteins through the extracellular region.

A, GP73 expression levels in hepatocytes in the course of acute and chronic liver disease. Normal hepatocyte GP73 expression is minimal. Marked and reversible increases in the percentage of GP73‐positive hepatocytes, and their cellular GP73 levels occur in acute hepatitis. Progressive up‐regulation is also observed in chronic liver disease and can be reversed by treatment of underlying disease aetiology (ie, steroid treatment of autoimmune hepatitis) and resolution of chronic hepatitis. GP73 expression in hepatocellular cancer cells is further increased (2‐ to 3‐fold) in comparison with patients with cirrhosis. B, Structural features of GP73 and sGP73. GP73 consists of a short cytoplasmic N‐terminus with a myristoylation domain followed by a single TM and large C‐terminal ectodomain. The N‐terminus contains two coiled‐coil domains and is N‐glycosylated. The C‐terminus is highly acidic of unknown function. Furin cleavage after aa 55 results in the extracellular release of sGP73. aa, amino acid; ELISA, enzyme‐linked immunosorbent assay; GP73, Golgi protein 73; HCC, hepatocellular carcinoma; sGP73, serum form of Golgi protein 73; TM, transmembrane domain103

2.3. Expression and distribution of GP73

The GP73 promoter −2618 bp/−19 bp has specificity for epithelial cells, so GP73 is widely expressed in almost all epithelial cells.14, 95, 97, 98, 99, 100, 101, 102, 103 Results from immunohistochemistry have also shown that the GP73 protein can be expressed in many types of cells in normal human tissues, but most important is epithelial cells, where the expression levels are very different. The difference may be up to 20 times.9, 77, 104, 105, 106, 107, 108 GP73 mRNA is expressed at higher levels in bronchial, gastric, colonic and prostate tissues, but with lower or no expression in muscle, white blood cells, lymphoid tissues and hearts.72, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118 The most densely expressed GP73 site is the digestive tract. It is also expressed in bile duct epithelial cells, tubular monolayer epithelial cells, pulmonary bronchioles, islets and hippocampus.

The high expression of GP73 belongs to epithelial cells, and these parts have well‐developed Golgi apparatus whose cells have strong secretory ability.9, 119, 120, 121, 122, 123, 124 GP73 is mainly expressed in normal liver tissue by bile duct epithelial cells in the portal area. This site is typical for the Golgi apparatus in epithelial cells but it has less or no expression in normal liver cells.125, 126, 127, 128, 129 However, in the presence of adenovirus infection, HBV or cancer, the expression level of GP73 in the bile duct cells is not changed significantly, but it is consistently high in liver cells, which increases the expression of GP73. These results indicate that hepatocytes undergo some transformation when liver diseases occur, altering some of the factors that regulate the expression of GP73. Studying these regulatory mechanisms will thus help to understand pathogenesis of liver diseases.130, 131, 132, 133, 134, 135, 136

2.4. Influencing factors for GP73 expression

GP73 expression is affected by many factors, such as viral infections, for example, the GP73 expression is increased in adenovirus‐infected HepG2 cells. The GP73 protein and mRNA expression are also increased after adenovirus‐infected Hep3B liver cancer cells. The expression level of GP73 is no longer increased under lack of adenovirus E1A domain, indicating that the GP73 expression is associated with adenovirus infection.137, 138, 139, 140 The expression of GP73 is also increased in HBV‐replicated cells, whereas the expression of GP73 does not increase in cells transfected with HBV but without HBV replication, indicating that HBV replication may stimulate the expression of GP73, and hence, the GP73 expression is associated with HBV replication.141 Moreover, studies have shown that the GP73 expression levels are increased in HBV and HCV infections, giant cell hepatitis and alcoholic hepatitis. The expression level of GP73 is also increased in SK‐Hep‐1 cells fed with IFN‐γ, while it is decreased in cells added with IFN‐α. In addition, IL‐6 and IL‐1 can raise the GP73 expression, and TGF‐β can reduce the expression of GP73.141 Studies by Song et al showed that the Hsp90 inhibitor IPI‐504 can affect the expression of many tumour‐associated proteins and genes in pancreatic cancer. The amount of GP73 was found by to be decreased by immunohistochemistry, mass spectrometry and gene expression profiling.142, 143, 144

2.5. Functions of GP73

At present, the biological function of GP73 is not fully understood. The Golgi apparatus is a complex processing centre in the cell, and its abnormal function is closely related to occurrence and development of many diseases, such as muscular dystrophy and defects of innate glycoprotein glycosylation.145, 146 GP73 is located in the Golgi apparatus, so GP73 is very likely to be closely related to the structure and functions of Golgi apparatus, which are intracellular transport, protein modification and signal transduction. Studies have shown that the acidic and coiled‐coil domains in the C‐terminal domain are the main domains for GP73 protein expression; truncation of C‐terminal acidic domain of GP73 can lead to significant reduction of survival rates in mice.147 Various degrees of liver disease and kidney disease also be happened; for example, the GP73 C‐terminal coiled‐coil domain can bind sCLU to assist its post‐translational modification and delivery functions, and it can also bind apolipoprotein E to promote hepatitis C virus secretion.148, 149 The −2618 bp/−19 bp promoter at the GP73 gene level is closely related to biological function of GP73, and the GC box in its promoter can regulate the transactivation of adenovirus E1A, providing a basis for activation of adenovirus E1A. The core promoter contains a CpG island in the promoter region of housekeeping gene, suggesting that the GP73 may have functional part in the housekeeping genes.51 According to distribution of GP73, its phenotype and physiological functions are mainly concentrated in the regulation of digestive system, hippocampus and blood glucose. GP73 is lowly expressed in normal hepatocytes, and its high expression in liver diseases indicates that GP73 levels may be associated with liver stress conditions. Monitoring of GP73 expression in patients with liver disease may indicate liver abnormalities and can determine the patient's liver repair status and repair capacity.150

3. DETECTION METHODS FOR GP73

At present, the detection methods for biomarkers are attracting more and more attention,151, 152, 153 and the methods for examining the GP73 include Western blot, immunohistochemical staining and ELISA. Chen et al154 used Western blot to detect GP73 in the serum of healthy people and liver cancer patients, and they found that the sensitivity was 78% and specificity was 93.5% when incubated with polyclonal antibodies. The sensitivity when incubated with monoclonal antibodies was 84.7%, and specificity of 93.5%. The stability and reproducibility of monoclonal antibodies are better than that of polyclonal antibodies. However, due to complicated operation of Western blot, it is difficult to be widely used in clinical practice.

Yao et al155 used immunohistochemical staining for detection of GP73, and their results showed that the sensitivity was 75.4% and specificity was 82.8%. The sensitivity was lower than that of serological tests but the immune response from the diseased tissue could be visually observed. However, Western blot and immunohistochemistry methods are cumbersome, complicated, and their price is expensive, so they are not suitable for detection of large clinical samples. There is therefore still a need to find a simple, fast and inexpensive GP73 detection method suitable for clinical large sample detection.

Gu et al156 used ELISA to detect expression level of GP73 in the serum with 82% sensitivity and 80% specificity, and the ratio of GP73 in healthy people and liver disease patients was 1:3. However, there was no significant difference in GP73 levels in patients with hepatocellular carcinoma (HCC), cirrhosis and hepatitis, so the ELISA method could not meet the detection for liver cancer. Beijing Hotview Company invented a kit for the detection of serum GP73 using ELISA method. It has since been used in clinical practice in China. As a tool for judging liver fibrosis and cirrhosis, its sensitivity is 62.8% and its specificity is 80.5%.

In addition, nanomaterials have represented perfectly suitable materials for a variety of biomedical and biotechnological applications.157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172 Our research group also established a variety of methodological detection methods. We used magnetic nanoparticle enzyme‐linked immunosorbent assay to detect serum GP73 levels in 79 cases of liver cancer and 64 healthy people. The sensitivity from our method was 78.43%, and specificity was 91.47%.173 In addition, the GP73 content in serum from 80 cases of liver cancer and 80 healthy people was detected by latex‐enhanced immunoturbidimetric method based on polyclonal antibody, with 94.6% sensitivity and 72.4% specificity. The use of three monoclonal antibody‐based latex‐enhanced immunoturbidimetric assays has a 96.7% sensitivity and 93.3% specificity.2 These two methods can be more easily automated, and they are faster than ELISA therefore have very good clinical application prospects.

4. RELATIONSHIP BETWEEN GP73 AND LIVER DISEASES

4.1. Relationship between GP73 and hepatitis

When liver cells develop autoimmune hepatitis or are infected with hepatitis B virus or hepatitis C virus, their GP73 expression levels will increase. When HBV and HCV are infected, the expression of GP73 in hepatocytes is increased significantly and do not change in the bile duct cells, suggesting that the active replication of hepatitis virus may be an important factor in the expression of GP73 in hepatocytes.174 Kladney et al175 found in 2000 that the GP73 expression increased during the progression of cirrhosis in autoimmune hepatitis, alcoholic liver disease, hepatitis B and liver disease. Iftikhar et al detected expression levels of GP73 in patients with autoimmune hepatitis, alcoholic liver disease, acute hepatitis and chronic hepatitis using Western blot, immunohistochemistry and immunofluorescence. They found that the GP73 levels increased in patients with liver disease, and GP73 levels in hepatocytes with alcoholic liver disease and chronic hepatitis were related to stage of the disease, regardless of the grade. Cells with alpha‐smooth muscle actin‐positive cells in liver sinusoidal endothelial cells also expressed GP73, suggesting that GP73 may be derived from activated hepatic stellate cells. In summary, they speculated that the secondary injury of chronic liver disease and the trigger mechanism for acute liver injury may lead to the expression of GP73.140 Wei et al found that the GP73 content in patients with chronic hepatitis C and HIV‐1 infection was significantly higher than that of healthy control group, and the increased GP73 was significantly correlated with body immune level and virus replication in HIV‐1‐infected patients. Therefore, patients with hepatitis C had too high GP73 and may not only be end‐stage liver disease or liver cancer and may also be combined with HIV‐1 infection, which also provides clinical clues for reference.176

4.2. Relationship between GP73 and cirrhosis

Liver cirrhosis is generally an end‐stage manifestation that occurs on the basis of diffuse liver damage, generally consisting of two mechanisms, namely, I: hepatocyte regeneration and proliferation of nodules; II: fibrous tissue proliferation and fibrous nodule formation, reconstruction of the original liver tissue and blood vessels. From hepatitis to liver fibrosis, liver cirrhosis and liver cancer are long and difficult to find process, and even if the alpha‐fetoprotein (AFP) detection abnormalities, but the imaging confirmation takes months or longer. Clinically, it is considered that 3 cm of HCC is an important demarcation point that is related to the prognosis. It takes at least 5 months for the tumour to grow from 1 cm to 3 cm, which means that the tumour can be detected after 5 months. The early diagnosis has important value for patient's treatment and prognosis.92 The study found that the expression level of GP73 in the liver cells increased significantly in patients with liver cirrhosis. Some scholars have studied 229 healthy people, liver cancer, liver cirrhosis and hepatitis patients and found GP73 expression levels in liver cancer and liver cirrhosis patients were significantly higher than in the healthy control group and hepatitis group.34 However, in another 535 studies, the GP73 expression levels in patients with cirrhosis were significantly higher than those in patients with liver cancer and hepatitis, and in the Child‐Pugh classification of cirrhosis, the GP73 levels were significantly higher in patients with grade B and grade C than those with grade A patients.92

Kladney et al used Western blot to analyse differences in GP73 content between cirrhosis and healthy subjects caused by different causes, including 17 healthy subjects, seven cases of autoimmune cirrhosis, nine cases of alcoholic cirrhosis and 14 patients with chronic hepatitis B cirrhosis and 23 patients with chronic hepatitis C cirrhosis. Their results found that the GP73 expression was elevated in patients with cirrhosis caused by different causes, but GP73 expression was not increased in healthy controls. The expression of GP73 in patients with cirrhosis caused by HBV was significantly increased by about 70 times. The level of GP73 in patients with cirrhosis, autoimmune cirrhosis and alcoholic cirrhosis caused by HCV was also elevated, but the level was not obvious. Their results suggested that the GP73 may play a crucial role in the pathogenesis of liver disease, but the specific mechanism is not yet clear.177

4.3. Relationship between GP73 and liver cancer

At present, GP73 has attracted more and more attention as a serological marker for liver cancer.178 Most of the studies suggest that GP73 can improve the diagnostic rate for liver cancer (Table 1), and its sensitivity and specificity are higher than that of AFP, a traditional hepatoma serum marker. However, there is also controversy. Block et al used glycoproteomics to find that GP73 serum levels in American cornfields with HCC in 2005 were significantly higher than those without HCC, and GP73 levels in patients with HCC were significantly higher than those in patients with colon metastases and HBV infection.183 Marrero et al detected GP73 serum levels in 352 liver cancer patients, liver cirrhosis patients and healthy subjects using Western blot (Figure 2). Their results showed that GP73 serum levels in liver cancer patients were significantly higher than those in patients with liver cirrhosis. Compared with AFP, the area under the receiver operating characteristic (ROC) curve for GP73 was 0.79, which was significantly larger than the area under the ROC curve for AFP of 0.61. In the case of cut‐off for 10 times relative units, the sensitivity of GP73 was 69% and specificity was 75%, while the sensitivity for AFP was 30% and specificity was 96%. And when the AFP level was 100 and 20 ng/mL, the patients who exceeded the optimal cut‐off value were more than 71% and 62%, respectively, thus showing that the use of GP73 was more valuable in cases where the increased level of AFP is not significant or does not increase.184

Table 1.

Detection methods and cut‐off values of GP73 in hepatocellular carcinoma (HCC) patients and controls

Methods	Patients with HCC/controls	Cut‐off values	References
Western blotting	13/93	7.4 relative units (RU)	180
Immunoblotting	102/179	8.5 RU	180
Immunoblotting	789/3428	8.5 RU	181
Immunoblotting	84/173	8.5 RU	104
ELISA	73/107	100 μg/L	29
ELISA	70/159	94.7 μg/L	182
ELISA	84/173	78.1 ng/L	4
Magnetic enzyme‐linked immunoassay	79/64	124.56 ng/mL	172
Monoclonal antibody‐based latex particle‐enhanced turbidimetric immunoassay	80/80	109.6 ng/mL	2
Polyclonal antibody‐based latex particle‐enhanced turbidimetric immunoassay	80/80	119.3 ng/mL	3

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Immunoblot analysis of GP73 levels in controls, cirrhosis and hepatocellular carcinoma (HCC). The top panel shows immunoblot analyses of sera from controls without liver disease, the middle panel from cirrhosis and lower panel from subjects with HCC 184

Hu et al182 studied the GP73 levels in 124 patients and found that the GP73 protein levels in patients with hepatitis‐related liver cancer were significantly higher than those in other liver diseases and healthy controls. The area under the ROC curve was 0.89, sensitivity was 77.4%, and specificity was 83.9%. After GP73 RNA was studied, the area under the ROC curve was 0.92, sensitivity was 87.1%, and specificity was 83.9%, indicating that the GP73 RNA detection was superior to GP73 protein detection. The detection of AFP revealed that the area under the ROC curve was 0.77, sensitivity was 48.4%, and specificity was 96.8%, indicating that the sensitivity for AFP detection was not as good as that of GP73.

Yu et al185 developed an electrochemical immunosensor for assaying of Golgi Protein 73 (GP73), which is a newly established and highly sensitive biomarker for biliary tract cancer. Intrinsic specificity and sensitivity of this immunosensor can be achieved due to good conductivity of electrochemically reduced graphene oxide, and prominent electrochemical signal of quantum dots. So, our sensor can enable a limit of detection as low as 12 pmol/L, and it can make direct serum assay possible. Results from this assay may clearly predict the effect of surgical removal of primary tumour, indicating potential clinical application of our sensor in the future (Figure 3).

Mao et al186 investigated the relationships between GP73 levels and tumour size or differentiation status or liver function. For comparison, AFP values for different tumour sizes or differentiation status or liver function were also analysed. The GP73 values were not correlated with tumour size, histological differentiation or Childe‐Pugh class. In contrast, the AFP values for patients with small HCCs (≤3 cm) were significantly less than that of other HCCs (≥5 cm, >3 and <5 cm, and diffuse HCC) (P < 0.001). GP73 was positive (≥8.5 relative units) in 30 of 34 (88.4%) AFP‐negative (<35 ng/mL) patients with small HCCs, while AFP was positive in three of seven (42.9%) GP73‐negative patients with small HCCs (Table 2). The sensitivity of GP73 for detection of liver cancer was 74.6%, and specificity was 97.4%, while the sensitivity of AFP for detection of liver cancer was 58.2% and specificity was 85.35%. This indicated that the GP73 was superior than AFP in detecting liver cancer. However, the combined diagnosis of GP73 and AFP is more likely to increase the detection rate of liver cancer (Figure 4). The diagnostic accuracy of serum GP73 and AFP in the same patient population was assessed in Table 3. The results demonstrated that GP73 showed higher sensitivity than AFP for HCC diagnosis. However, several studies showed the specificity of GP73 was lower than AFP, which might be due to that GP73 can be expressed in many types of cells, but the maior cell type was epithelial cells.

Table 2.

GP73 and alpha‐fetoprotein (AFP) of hepatocellular carcinoma (HCC) with different tumour sizes, differentiations and liver functions186

Tumour size (cm)	≤3 (n = 45)	>3 and <5 (n = 126)	≥5 (n = 197)	Diffuse (n = 55)
GP73 value (RU)	16.1 (10.6‐42.6)	14.1 (6.8‐42.6)	18.6 (12.3‐38.8)	17.6 (8.3‐35.1)
AFP (ng/mL)	29.8 (10.1‐34.9)[Link]	102.7 (11.2‐360.4)	129.6 (10.8‐353.2)	121.8 (11.0‐358.7)

Tumour differentiation	High (n = 52)	Moderate (n = 80)	Low (n = 48)
GP73 value (RU)	12.9 (7.4‐46.2)	19.0 (8.3‐39.3)	17.6 (9.9‐65.2)
AFP (ng/mL)	119.0 (20.8‐478.6)	129.8 (18.9‐442.5)	143.1 (12.9‐465.3)

Childe‐Pugh class	A (n = 221)	B (n = 162)	C (n = 43)
GP73 value (RU)	15.6 (10.2‐38.9)	14.6 (9.4‐41.2)	16.8 (11.0‐52.6)
AFP (ng/mL)	108.9 (14.0‐395.6)	122.6 (24.8‐410.2)	124.6 (22.1‐469.3)

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P < 0.001 vs >3 and <5, ≥5 and diffuse HCC.

Serum Golgi protein 73 (GP73) is increased in patients with hepatocellular carcinoma (HCC), with higher sensitivity and specificity than alpha‐fetoprotein (AFP). A, The GP73 values for HCC‐related diseases. The serum GP73 level for healthy subjects, patients with cirrhosis and patients with HCC was 1.2 (0.9e1.7) relative units (RU), 4.7 (2.6e8.0) RU and 14.7 (8.4e29.4) RU, respectively. ^§ P < 0.001 vs HCC and cirrhosis. B, The receiver operating characteristic (ROC) curve for combined AFP and GP73 in HCC diagnosis of all subjects. The points in the ROC curve indicate different GP73 values with corresponding sensitivity and specificity, from which the cut‐off value was chosen, and 8.5 RU (boxed) was the cut‐off value for GP73186

Table 3.

Comparison of sensitivity and specificity of alpha‐fetoprotein (AFP) and GP73 in hepatocellular carcinoma

Authors	No. of patients	AFP				GP73
Authors	No. of patients	Detection method	Cut‐off value	Sensitivity (%)	Specificity (%)	Detection method	Cut‐off value	Sensitivity (%)	Specificity (%)
Marrero et al184	352	Immunoassays utilizing enhanced chemiluminescence	112 ng/mL	25	97	Immunoblotting	10 relative units	62	88
Mao et al186	4217	Immunoassays utilizing enhanced chemiluminescence	35 ng/mL	58.2	85.3	Immunoblotting	8.5 relative units	74.6	97.4
Sai et al43	328	Immunoassays utilizing enhanced chemiluminescence	50 μg/L	71.97	84.48	ELISA	70 μg/L	78.34	77.59
Wang et al40	257	Immunoassays	13.5 relative units	60.7	75	Immunoblotting	13.5 relative units	82.1	80
Hou et al77	184	Chemiluminescence immunoassay	—	55.6	86.7	Time‐resolved fluorescence immunological assay	78.1 ng/L	73.4	79
Hu et al182	124	Electrochemiluminescence immunoassay	—	48.4	96.8	Western blotting	7.4 relative units	77.4	83.9

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Although GP73 has great potential as a diagnostic marker for liver cancer, there are still many differences. For example, most studies reported that the serum levels of GP73 in patients with liver cancer were higher than those in other liver diseases, but there were also some opposite results. Tian et al187 used ELISA to detect 535 samples, including liver metastatic adenocarcinoma, intrahepatic cholangiocarcinoma, hemangioma, focal hyperplasia, hepatitis, liver cirrhosis, liver cancer and healthy people. Their results showed that GP73 levels in cirrhotic patients were higher than those in patients with liver cancer and hepatitis. Gu et al156 detected serum GP73 by ELISA. Their results showed that the GP73 content of liver disease patients was higher than that of healthy control group, but there was no difference in the liver disease patients from each group. These differences may be related to individual differences in the subjects, sample collection, preservation differences, differences in reagent use, differences in detection methods and so on. Therefore, obtaining samples from different populations in different regions in the study, expanding the number of test samples and establishing more effective and reliable detection methods are of great value for accurate GP73 detection in liver cancer.

Besides, exosomes are 30‐100 nm secreted vesicles that have emerged as a novel mode of diagnostic marker and demonstrated to play important roles in cellular intercommunication. They are enriched in various bioactive materials, including proteins, lipids, miRNAs and mRNAs.188 Exosomes have also been found in several types of body fluids, including plasma, malignant effusions, urine, saliva and amniotic fluid.189 In addition to some common exosomal proteins such as TSG101, Alix, CD9, CD81, CD63 and cytoskeletal proteins including actin, and tubulin proteins, exosomes may carry some disease‐associated proteins for they are a sub‐part of originated cells.190 Several researches have shown that the GP73 protein is present in exosome surface.191, 192, 193, 194 The advantages of exosomes as tumour markers are as follows: (a) a large quantity, the concentration of exosomes in the serum can reach 3 × 10⁶ cells/μL.195 On average, each tumour cell can release 530 exosomes/24 hour196; (b) information rich and similar to tumour cells; the surface of exosomal membrane also has the same protein as cell membrane, which can represent characteristics and state of its parental cell197; (c) it is easy to preserve for a long time and remove interference; there is phospholipid bilayer to protect its degradation by proteases and nucleases, and as long as the separation of exosomes can remove the interference198; and (d) non‐invasive detection; exosomes can enter the circulatory system through endothelium and can therefore be detected in almost all body fluids.199 Compared to tissue biopsy, exosomes are effective biomarkers for personalized medicine. Therefore, analysis of GP73 protein in exosome surface will be valued in the diagnosis of liver cancer.

5. CHALLENGES AND STRATEGIES

In summary, the serum levels of GP73 in patients with liver diseases, such as hepatitis, liver cirrhosis and liver cancer, have increased in varying degrees. Although accumulating studies indicate that abnormal GP73 expression is associated with tumour progression by interacting with the microenvironment, and GP73 has been regarded as a potential diagnostic marker for HCC, the diagnosis accuracy of GP73 in cirrhosis and HCC distinguishment is worthy discussed.20, 22, 187 Although some studies found that ELISA result did not show a significant elevation of serum GP73 in HCC groups compared with that in liver cirrhosis groups. Recent reports described that GP73‐specific serum autoantibodies might interfere with ELISA analysis. Researchers have found several isoforms of GP73 that correspond with different patterns or levels of glycosylation.200, 201, 202 It still needs further research about the significance of HCC‐specific GP73 isoform in diagnostic accuracy improvement. Moreover, GP73 tends to be used as a useful biomarker to monitor HCC prognosis after primary tumour surgery and therapy in advanced HCC.132, 133 In terms of clinical application, it is still a new biomarker, and large‐scale and multi‐centred investigations are still needed. Moreover, more sensitive, specific and rapid diagnostic methods are also needed. Since exosomes have many advantages, and a new detection method for GP73 from the perspective of exosomes is imperative to enhance the role of GP73 in human health research.

ACKNOWLEDGEMENTS

This work was supported by National Natural Scientific Foundation of China (81700790, 81472831, 61527806 and 61741114), the Jiangsu Province Medical Talent (ZDRCA2016065), the Key Research and Development Project of Jiangsu Province (BE2016625), the Medical Key Science and Technology Development Projects of Nanjing (ZKX16045), the Science and Technology Development Program of Nanjing (201715020), the Health Care for Cadres Research Fund of Jiangsu Province (BJ16003), the Opening Project of State Key Laboratory of Bioelectronics (201705) and the Open Funding of State Key Laboratory of Oral Diseases (SKLOD2018OF02).

Xia Y, Zhang Y, Shen M, Xu H, Li Z, He N. Golgi protein 73 and its diagnostic value in liver diseases. Cell Prolif. 2019;52:e12538 10.1111/cpr.12538

Yanyan Xia and Yuanying Zhang contributed equally to this work.

Contributor Information

Zhiyang Li, Email: 29313783@qq.com.

Nongyue He, Email: nyhe1958@163.com.

REFERENCES

1. Xing BY, Qian C, Ying Y, et al. Expression and prognostic significance of Golgi glycoprotein 73 (GP73) with epithelial‐mesenchymal transition (EMT) related molecules in hepatocellular carcinoma (HCC). Diagn Pathol. 2013;8:197‐202. [DOI] [PMC free article] [PubMed] [Google Scholar]
2. Xia Y, Han S, Zhu Y, et al. A sensitive three monoclonal antibodies based automatic latex particle‐enhanced turbidimetric immunoassay for Golgi protein 73 detection. Sci Rep. 2017;7:40090‐40099. [DOI] [PMC free article] [PubMed] [Google Scholar]
3. Xia Y, Yao A, Xu H, et al. Comparison of two latex nanoparticles with different diameters and the application in detection of biomarker golgi protein 73 in hepatocellular carcinoma. Nanosci Nanotech Lett. 2017;9:398‐405. [Google Scholar]
4. Xu WF, Fei YM, Zhou JK, et al. Significance of serum golgi protein 73 (GP73), alpha‐fetoprotein (AFP) and lectin‐reactive alpha‐fetoprotein (AFP‐L3) expression in primary hepatic carcinoma. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2011;25:286‐288. [PubMed] [Google Scholar]
5. Yang Y, Liu Q, Zhang H, et al. Silencing of GP73 inhibits invasion and metastasis via suppression of epithelial‐mesenchymal transition in hepatocellular carcinoma. Oncol Rep. 2017;37:1182‐1188. [DOI] [PubMed] [Google Scholar]
6. Donizy P, Kaczorowski M, Biecek P, et al. Golgi‐related proteins GOLPH2 (gp73/golm1) and GOLPH3 (gopp1/midas) in cutaneous melanoma: patterns of expression and prognostic significance. Int J Mol Sci. 2016;17:1619‐1636. [DOI] [PMC free article] [PubMed] [Google Scholar]
7. Li XF, Wang GX, Huang TC, et al. Clinical application of gp73 for hepatocellular carcinoma with transarterial chemoembolization combined radiofrequency abolition. Basic Clin Pharmacol Toxicol. 2015;117:2. [Google Scholar]
8. Ibrahim GH, Mahmoud MA, Aly NM. Evaluation of circulating transforming growth factor‐beta 1, glypican‐3 and golgi protein‐73 mRNAs expression as predictive markers for hepatocellular carcinoma in Egyptian patients. Mol Biol Rep. 2013;40:7069‐7075. [DOI] [PubMed] [Google Scholar]
9. Weiskirchen R, Tacke F. Combining GP73 with liver stiffness measurements: a proof‐of‐concept for non‐invasive fibrosis assessment in antiviral‐naïve HBV patients. Liver Int. 2017;37:1605‐1607. [DOI] [PubMed] [Google Scholar]
10. Yang HJ, Liu GL, Liu B, et al. GP73 promotes invasion and metastasis of bladder cancer by regulating the epithelial–mesenchymal transition through the TGF‐β1/Smad2 signalling pathway. J Cell Mol Med 2018;22:1650‐1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
11. Ye JZ, Yan SM, Yuan CL, et al. GP73 level determines chemotherapeutic resistance in human hepatocellular carcinoma cells. J Cancer. 2018;9:415‐423. [DOI] [PMC free article] [PubMed] [Google Scholar]
12. Kawamoto S, Moriwaki K, Nakagawa T, et al. Overexpression of α1,6‐fucosyltransferase in hepatoma enhances expression of Golgi phosphoprotein 2 in a fucosylation‐independent manner. Int J Oncol. 2011;39:203‐208. [DOI] [PMC free article] [PubMed] [Google Scholar]
13. Wei H, Li B, Zhang R, et al. Serum GP73, a marker for evaluating progression in patients with chronic HBV infections. PLoS One. 2013;8:e53862‐e53869. [DOI] [PMC free article] [PubMed] [Google Scholar]
14. Katada T, Ishiguro H, Kimura M, et al. GP73, contributes to the sensitivity of cisplatin in esophageal cancer. Esophagus. 2009;6:173‐176. [Google Scholar]
15. Kai J, Wei L, Zhang Q, et al. GP73 N‐glycosylation at Asn144 reduces hepatocellular carcinoma cell motility and invasiveness. Oncotarget. 2016;7:23530‐23541. [DOI] [PMC free article] [PubMed] [Google Scholar]
16. Romano PR, Nikolaeva OV, Steel L, et al. 1261 GP73, a resident golgi membrane protein, appears in sera of patients with viral liver disease and hepatocellular cancer. Hepatology. 2003;38:768. [Google Scholar]
17. Almansour M, Sajti L, Melhim W, et al. Ultrastructural hepatic alterations induced by 35 nm zinc oxide nanoparticles. Nanosci Nanotech Lett. 2015;7:763‐769. [Google Scholar]
18. Russell WA, Owens JC, Peters DC, et al. Registration of maize germplasm (Reg. Nos. GP72 and GP73). Crop Sci. 1976;16:886. [Google Scholar]
19. Kai Z, Zhi D, Jian Z. Biomarkers for hepatocellular carcinoma: progression in early diagnosis, prognosis, and personalized therapy. Biomark Res. 2013;1:10. [DOI] [PMC free article] [PubMed] [Google Scholar]
20. Timothy B. The re‐emergence of the GP73 and fucosylated liver cancer biomarkers. Eng Sci. 2014;12:59‐64. [Google Scholar]
21. Liu X, Wan X, Lu S, et al. Evaluation of a magnetic particles‐based chemiluminescence enzyme immunoassay for Golgi protein 73 in human serum. Clin Chim Acta. 2015;445:54‐59. [DOI] [PubMed] [Google Scholar]
22. Zhang Y, Xi Y, Fang J, et al. Identification and characterization of monoclonal antibodies against GP73 for use as a potential biomarker in liver cancer screening and diagnosis. J Immunoassay Immunochem. 2016;37:390‐406. [DOI] [PubMed] [Google Scholar]
23. Zhao J, Xu T, Wang F, et al. Mir‐493‐5p suppresses hepatocellular carcinoma cell proliferation through targeting GP73. Biomed Pharmacother. 2017;90:744‐751. [DOI] [PubMed] [Google Scholar]
24. Di J, Tao J, Dan L, et al. Golgi protein 73 activation of MMP‐13 promotes hepatocellular carcinoma cell invasion. Oncotarget. 2015;6:33523‐33533. [DOI] [PMC free article] [PubMed] [Google Scholar]
25. Yang H, Xu H, Wang Y, et al. Clinicopathologic correlations of Golgi protein 73 and signal transducer and activator of transcription 3 expression in hepatocellular carcinoma. Transl Cancer Res. 2017;6:238‐246. [Google Scholar]
26. Hou X, Yang L, Jiang X, et al. Prognostic significance of golgi protein 73 in hepatocellular carcinoma after hepatectomy in the Chinese population: a meta‐analysis. Int J Clin Exp Med. 2017;10:48‐58. [Google Scholar]
27. Zhou N, Wang K, Fang S, et al. Discovery of a potential plasma protein biomarker panel for acute‐on‐chronic liver failure induced by hepatitis B virus. Front Physiol. 2017;8:1009‐1020. [DOI] [PMC free article] [PubMed] [Google Scholar]
28. Zhao J, Guo LY, Yang JM, et al. Sublingual vein parameters, AFP, AFP‐L3, and GP73 in patients with hepatocellular carcinoma. Genet Mol Res. 2015;14:7062‐7067. [DOI] [PubMed] [Google Scholar]
29. Shi Y, Chen J, Li L, et al. A study of diagnostic value of golgi protein GP73 and its genetic assay in primary hepatic carcinoma. Technol Cancer Res Treat. 2011;10:287‐294. [DOI] [PubMed] [Google Scholar]
30. Yamamoto K, Imamura H, Matsuyama Y, et al. AFP, AFP‐L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC. J Gastroenterol. 2010;45:1272‐1282. [DOI] [PubMed] [Google Scholar]
31. Zhang YL, Zhang YC, Han W, et al. Effect of GP73 silencing on proliferation and apoptosis in hepatocellular cancer. World J Gastroenterol. 2014;20:11287‐11296. [DOI] [PMC free article] [PubMed] [Google Scholar]
32. Yang M, Guan Y, Yang Y, et al. Immunological detection of hepatocellular carcinoma biomarker GP73 based on dissolved magnetic nanoparticles. Colloids Surf A Physicochem Eng Asp. 2014;443:280‐285. [Google Scholar]
33. Ozal G, Akbulut H, Akgun N, et al. Golgi protein 73 (gp73) is a useful tumor marker in patients with colon cancer. J Clin Oncol. 2011;29:2696.21606413 [Google Scholar]
34. Dong M, Chen ZH, Li X, et al. Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma. Oncol Lett. 2017;14:6277‐6284. [DOI] [PMC free article] [PubMed] [Google Scholar]
35. Morota K, Nakagawa M, Sekiya R, et al. A comparative evaluation of Golgi protein‐73, fucosylated hemopexin, α‐fetoprotein, and PIVKA‐II in the serum of patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Clin Chem Lab Med. 2011;49:711‐718. [DOI] [PubMed] [Google Scholar]
36. Yuan Y, Shi L, Wang S. Expression and correlation of CD44 and GP73 in cerebroma tissues. Oncol Lett. 2018;15:4958‐4962. [DOI] [PMC free article] [PubMed] [Google Scholar]
37. Yang SL, Zeng C, Fang X, et al. Hepatitis B virus upregulates GP73 expression by activating the HIF‐2α signaling pathway. Oncol Lett. 2018;15:5264‐5270. [DOI] [PMC free article] [PubMed] [Google Scholar]
38. Hull C, Regehr AWG. Identification of an inhibitory circuit that regulates cerebellar golgi cell activity. Neuron. 2012;73:149‐158. [DOI] [PMC free article] [PubMed] [Google Scholar]
39. Jiang JC, Zhou LF. Advances on Golgi glycoprotein 73 and its association with diseases. J Zhejiang Univ. 2012;41:215‐221. [DOI] [PubMed] [Google Scholar]
40. Wang Y, Yang H, Xu H, et al. Golgi protein 73, not Glypican‐3, may be a tumor marker complementary to α‐Fetoprotein for hepatocellular carcinoma diagnosis. J Gastroenterol Hepatol. 2014;29:597‐602. [DOI] [PubMed] [Google Scholar]
41. Wang F, Li Z, Li L, et al. GP73 was upregulated in PBMC stimulated with ConA but failed to promote lymphocyte proliferation. Cell Biol Int. 2015;39:334‐340. [DOI] [PubMed] [Google Scholar]
42. Castaldo G, Monaco L, Castaldo L, et al. An observational study of sequential protein‐sparing, very low‐calorie ketogenic diet (Oloproteic diet) and hypocaloric Mediterranean‐like diet for the treatment of obesity. Int J Food Sci Nutr. 2016;67:696‐706. [DOI] [PubMed] [Google Scholar]
43. Sai W, Wang L, Zheng W, et al. Abnormal expression of Golgi protein 73 in clinical values and their role in HBV‐related hepatocellular carcinoma diagnosis and prognosis. Hepat Mon. 2015;15:e32918. [DOI] [PMC free article] [PubMed] [Google Scholar]
44. Tian SB, Yu JC, Kang WM, et al. Combined detection of CEA, CA 19‐9, CA 242 and CA 50 in the diagnosis and prognosis of resectable gastric cancer. Asian Pac J Cancer Prev. 2014;15:6295‐6300. [DOI] [PubMed] [Google Scholar]
45. Li J, Wang B, Gu S, et al. Amperometric low potential aptasensor for the fucosylated Golgi protein 73, a marker for hepatocellular carcinoma. Microchim Acta. 2017;184:1‐6. [Google Scholar]
46. Tunissiolli NM, Castanhole‐Nunes MMU, Biselli‐Chicote PR, et al. Hepatocellular carcinoma: a comprehensive review of biomarkers, clinical aspects, and therapy. Asian Pac J Cancer Prev. 2017;18:863‐872. [DOI] [PMC free article] [PubMed] [Google Scholar]
47. Moustafa TA, Aly MM, Abu‐Zahab Z, et al. Evaluation of erythropoietin level in vitreous and serum with detection of erythropoietin gene polymorphism in Egyptian patients with proliferative diabetic retinopathy. Egypt Retina J. 2017;4:71‐76. [Google Scholar]
48. Zhang A, Cao B. Brian. Generation and characterization of an anti‐GP73 monoclonal antibody for immunoblotting and sandwich ELISA. J Biomed Mater Res. 2012;26:467‐473. [DOI] [PMC free article] [PubMed] [Google Scholar]
49. Li L, Wen L, Gong Y, et al. Xenopus as a model system for the study of GOLPH2/GP73 function: Xenopus GOLPH2 is required for pronephros development. PLoS One. 2012;7:e38939. [DOI] [PMC free article] [PubMed] [Google Scholar]
50. Li QW, Chen HB, Li ZY, et al. Preparation and characterization of Anti‐GP73 monoclonal antibodies and development of double‐antibody sandwich ELISA. Asian Pac J Cancer Prev. 2015;16:2043‐2049. [DOI] [PubMed] [Google Scholar]
51. Wang NY, Wang C, Li W, et al. Prognostic value of serum AFP, AFP‐L3, and GP73 in monitoring short‐term treatment response and recurrence of hepatocellular carcinoma after radiofrequency ablation. Asian Pac J Cancer Prev. 2014;15:1539‐1544. [DOI] [PubMed] [Google Scholar]
52. Liu H, Li P, Zhai Y, et al. Diagnostic value of glypican‐3 in serum and liver for primary hepatocellular carcinoma. World J Gastroenterol. 2010;16:4410‐4415. [DOI] [PMC free article] [PubMed] [Google Scholar]
53. Kladney RD, Bulla GA, Guo L, et al. GP73, a novel Golgi‐localized protein upregulated by viral infection. Gene. 2000;249:53‐65. [DOI] [PMC free article] [PubMed] [Google Scholar]
54. Li J, Cheng ZJ, Liu Y, et al. Serum thioredoxin is a diagnostic marker for hepatocellular carcinoma. Oncotarget. 2015;6:9551‐9563. [DOI] [PMC free article] [PubMed] [Google Scholar]
55. He Q, Li JK, Li F, et al. Mechanism of action of gypenosides on type 2 diabetes and non‐alcoholic fatty liver disease in rats. World J Gastroenterol. 2015;21:2058‐2066. [DOI] [PMC free article] [PubMed] [Google Scholar]
56. Guan Y, Li A, Xiao W, et al. The efficacy and safety of Endostar combined with chemoradiotherapy for patients with advanced, locally recurrent nasopharyngeal carcinoma. Oncotarget. 2015;6:33926‐33934. [DOI] [PMC free article] [PubMed] [Google Scholar]
57. Ni R, Xiao M, Jin F, et al. Clinical value of hepatoma‐specific Alpha‐fetoprotein in the diagnosis of hepatocellular carcinoma. Cancer Bio Med. 2006;3:153‐157. [Google Scholar]
58. Jiang K, Li W, Shang S, et al. Aberrant expression of Golgi protein 703 is indicative of a poor outcome in hepatocellular carcinoma. Oncol Rep. 2016;35:2141‐2150. [DOI] [PubMed] [Google Scholar]
59. Lu XL, Liang X, Zhang YX, et al. Saikosaponin D inhibits proliferation and induces apoptosis via C/EBPβ‐p53 signal pathway in human hepatoma HepG2 cells. J Pharm Anal. 2010;22:252‐254. [Google Scholar]
60. Jing JS, Ye W, Jiang YK, et al. The value of GPC3 and GP73 in clinical diagnosis of hepatocellular carcinoma. Clin Lab. 2017;63:1903‐1909. [DOI] [PubMed] [Google Scholar]
61. Liu LP, Chen JK, Liu YM, et al. Depletion of GP73 inhibits invasion and metastasis of hepatocellular carcinoma cells. Zhonghua Zhong Liu Za Zhi. 2017;39:497‐501. [DOI] [PubMed] [Google Scholar]
62. Zhang X, Meng S, Zhang R, et al. GP73‐regulated oncolytic adenoviruses possess potent killing effect on human liver cancer stem‐like cells. Oncotarget. 2016;7:29346‐29358. [DOI] [PMC free article] [PubMed] [Google Scholar]
63. Cao Z, Li Z, Liu Y, et al. A novel non‐invasive Golgi protein 73 (GP73)‐based model accurately diagnoses significant fibrosis in chronic liver disease. J Hepatol. 2017;66:S677. [DOI] [PubMed] [Google Scholar]
64. Ai N, Liu W, Li ZG, et al. High expression of GP73 in primary hepatocellular carcinoma and its function in the assessment of transcatheter arterial chemoembolization. Oncol Lett. 2017;14:3953‐3958. [DOI] [PMC free article] [PubMed] [Google Scholar]
65. Shek FH, Lai TCW, Fatima S, et al. Oncofetal molecules as biomarkers and drug targets for hepatic cancer New Advances on Disease Biomarkers & Molecular Targets in Biomedicine. Totowa, NJ: Humana Press; 2013:57‐74. [Google Scholar]
66. Tat TN, Duong DC, Tong HV, et al. Optimisation of quantitative miRNA panels to consolidate the diagnostic surveillance of HBV‐related hepatocellular carcinoma. PLoS One. 2018;13:e0196081. [DOI] [PMC free article] [PubMed] [Google Scholar]
67. Kang C, Xu R, Xu F, et al. The value of dynamic combined detection of serum tumor biomarkers in diagnosing primary hepatic carcinoma. Cancer Res Clin. 2014;26:531‐534. [Google Scholar]
68. Zhang X, Wang T, Dai X, et al. Golgi protein 73 facilitates the interaction of hepatitis C virus NS5A with apolipoprotein E to promote viral particle secretion. Biochem Biophys Res Commun. 2016;479:683‐689. [DOI] [PubMed] [Google Scholar]
69. Hu GS, Li YQ, Yang YM, et al. High expression of Golgi phosphoprotein‐3 is associated with poor survival in patients with hepatocellular carcinoma. Tumor Biol. 2014;35:8625‐8632. [DOI] [PubMed] [Google Scholar]
70. Mao YL, Yang HY, Xu HF, et al. Significance of Golgi glycoprotein 73, a new tumor marker in diagnosis of hepatocellular carcinoma: a primary study. Zhonghua Yi Xue Za Zhi. 2008;88:948‐951. [PubMed] [Google Scholar]
71. Li B, Li B, Guo T, et al. The clinical values of serum markers in the early prediction of hepatocellular carcinoma. Biomed Res Int. 2017;2017:5358615. [DOI] [PMC free article] [PubMed] [Google Scholar]
72. Bachert C, Fimmel C, Linstedt AD. Endosomal trafficking and proprotein convertase cleavage of cis Golgi protein GP73 produces marker for hepatocellular carcinoma. Traffic. 2007;8:1415‐1423. [DOI] [PubMed] [Google Scholar]
73. Xia FD, Wang ZL, Chen HX, et al. Differential expression of IQGAP1/2 in hepatocellular carcinoma and its relationship with clinical outcomes. Asian Pac J Cancer Prev. 2014;15:4951‐4956. [DOI] [PubMed] [Google Scholar]
74. Li W, Qi K, Wang Z, et al. Golgi phosphoprotein 3 regulates metastasis of prostate cancer via matrix metalloproteinase 9. Int J Clin Exp Pathol. 2015;8:3691‐3700. [PMC free article] [PubMed] [Google Scholar]
75. Donizy P, Biecek P, Halon A, et al. Nucleoli cytomorphology in cutaneous melanoma cells‐a new prognostic approach to an old concept. Diagn Pathol. 2017;12:88‐96. [DOI] [PMC free article] [PubMed] [Google Scholar]
76. Xu Z, Liu L, Pan X, et al. Serum Golgi protein 73 (GP73) is a diagnostic and prognostic marker of chronic HBV liver disease. Medicine. 2015;94:e659. [DOI] [PMC free article] [PubMed] [Google Scholar]
77. Hou S, Xiao M, Runzhou NI, et al. Serum GP73 is complementary to AFP and GGT‐II for the diagnosis of hepatocellular carcinoma. Oncol Lett. 2013;6:1152‐1158. [DOI] [PMC free article] [PubMed] [Google Scholar]
78. Mehta A, Herrera H, Block T. Chapter seven – glycosylation and liver cancer. Adv Cancer Res. 2015;126:257‐279. [DOI] [PMC free article] [PubMed] [Google Scholar]
79. Liang R, Chen XY, Ge LY, et al. Meta‐analysis supports the diagnostic value of GP73 in primary liver cancer. Clin Res Hepatol Gastroenterol. 2015;39:71‐72. [DOI] [PubMed] [Google Scholar]
80. Yao M, Wang L, Psc L, et al. The clinical significance of gp73 in immunologically mediated chronic liver diseases: experimental data and literature review. Clin Rev Allergy Immunol. 2017;2017:1‐13. [DOI] [PubMed] [Google Scholar]
81. Zhao Y, Wang M, Cui C, et al. Significance of combined tests of serum golgi glycoprotein 73 and other biomarkers in diagnosis of small primary hepatocellular carcinoma. Cancer Biomark. 2016;15:677‐683. [DOI] [PMC free article] [PubMed] [Google Scholar]
82. Huo Q, Zheng Z, Liu J, et al. Diagnosis value of combined detection of serum golgi protein 73, desgamma carboxy prothrombin and α‐fetoprotein in primary hepatic carcinoma. Zhonghua Yi Xue Za Zhi. 2015;95:757‐760. [PubMed] [Google Scholar]
83. Cheng J, Wang W, Zhang Y, et al. Prognostic role of pre‐treatment serum AFP‐l3% in hepatocellular carcinoma: systematic review and meta‐analysis. PLoS One. 2014;9:e87011. [DOI] [PMC free article] [PubMed] [Google Scholar]
84. Malaguarnera G, Giordano M, Paladina I, et al. Serum markers of hepatocellular carcinoma. Digest Dis Sci. 2010;55:2744‐2755. [DOI] [PubMed] [Google Scholar]
85. Cao Z, Li Z, Wang Y, et al. Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection. J Viral Hepatitis. 2017;24:57‐65. [DOI] [PubMed] [Google Scholar]
86. Yuan L, Zou Z, Bing Z, et al. CXCL10 decreases GP73 expression in hepatoma cells at the early stage of hepatitis c virus (HCV) infection. Int J Mol Sci. 2013;14:24230‐24241. [DOI] [PMC free article] [PubMed] [Google Scholar]
87. Wei H, Zhang J, Li H, et al. GP73, a new marker for diagnosing HBV‐ACLF in population with chronic HBV infections. Diagn Micr Infec Dis. 2014;79:19‐24. [DOI] [PubMed] [Google Scholar]
88. Zhou YY, Jiang JC, You J, et al. Effect of Golgi phosphoprotein 2 (GOLPH2/GP73) on autophagy in human hepatocellular carcinoma HepG2 cells. Tumor Biol. 2015;36:3399‐3406. [DOI] [PubMed] [Google Scholar]
89. Zhang ZQ, Meng H, Wang N, et al. Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol. 2014;9:135‐141. [DOI] [PMC free article] [PubMed] [Google Scholar]
90. Hu B, Tian X, Sun J, et al. Evaluation of individual and combined applications of serum biomarkers for diagnosis of hepatocellular carcinoma: a meta‐analysis. Int J Mol Sci. 2013;14:23559‐23580. [DOI] [PMC free article] [PubMed] [Google Scholar]
91. Chiappini F. Circulating tumor cells measurements in hepatocellular carcinoma. Int J Hepatol. 2012;2012:684802‐684817. [DOI] [PMC free article] [PubMed] [Google Scholar]
92. Yong Q, Chen J, Xin L, et al. Serum gp73 is also a biomarker for diagnosing cirrhosis in population with chronic HBV infection. Clin Biochem. 2014;47:216‐222. [DOI] [PubMed] [Google Scholar]
93. Qiao SS, Cui ZQ, Gong L, et al. Simultaneous measurements of serum AFP, GPC‐3 and HCCR for diagnosing hepatocellular carcinoma. Hepatogastroenterology. 2011;58:1718‐1724. [DOI] [PubMed] [Google Scholar]
94. Pillai AA, Fimmel CJ. Emerging serum biomarkers of HCC. Primary Liver Cancer. 2012;2012:247‐262. [Google Scholar]
95. Liu G, Zhang Y, He F, et al. Expression of GOLPH2 is associated with the progression of and poor prognosis in gastric cancer. Oncol Rep. 2014;32:2077‐2085. [DOI] [PubMed] [Google Scholar]
96. Arora G, Flores R, Wright L, et al. Abstract 1323: Liver‐specific knockout mice and liver‐derived cell lines provide insights into potential roles for the GP73/GOLM1 HCC serum biomarker ‐ association with sustained cell proliferation. J Cancer Res. 2012;72:1323. [Google Scholar]
97. Jiang K, Shang S, Li W, et al. Multiple lectin assays for detecting glyco‐alteration of serum GP73 in liver diseases. Glycoconj J. 2015;32:657‐664. [DOI] [PubMed] [Google Scholar]
98. Ozkan H, Erdal H, Tutkak H, et al. Diagnostic and prognostic validity of Golgi protein 73 in hepatocellular carcinoma. Digestion. 2012;86:83‐88. [DOI] [PubMed] [Google Scholar]
99. Tan LY. Correlation between GP73 protein and human liver disease. Zhonghua Gan Zang Bing Za Zhi. 2007;15:958‐959. [PubMed] [Google Scholar]
100. Wang M, Long RE, Comunale MA, et al. Analysis of GP73 in combination with fucosylated alpha‐1‐antitrypsin and fucosylated kininogen as a biomarker of primary hepatocellular carcinoma. Cancer Biomark. 2008;4:155. [Google Scholar]
101. Sun S, Day PJ, Lee NP, et al. Biomarkers for early detection of liver cancer: focus on clinical evaluation. Protein Pept Lett. 2009;16:473‐478. [DOI] [PubMed] [Google Scholar]
102. Naryshkina T, Liu J, Florens L, et al. Thermus thermophilus bacteriophage phiYS40 genome and proteomic characterization of virions. J Mol Biol. 2006;364:667‐677. [DOI] [PMC free article] [PubMed] [Google Scholar]
103. Fimmel CJ, Wright L. Golgi protein 73 as a biomarker of hepatocellular cancer: development of a quantitative serum assay and expression studies in hepatic and extrahepatic malignancies. Hepatology. 2009;49:1421‐1423. [DOI] [PubMed] [Google Scholar]
104. Wang MJ, Long RE, Comunale MA, et al. Novel fucosylated biomarkers for the early detection of hepatocellular carcinoma. Cancer Epidermiol Biomarkers Prev. 2009;18:1914‐1921. [DOI] [PMC free article] [PubMed] [Google Scholar]
105. Andreana L, Isgrò G, Pleguezuelo M, et al. Surveillance and diagnosis of hepatocellular carcinoma in patients with cirrhosis. World J Hepatol. 2009;1:48‐61. [DOI] [PMC free article] [PubMed] [Google Scholar]
106. Xu Z, Shen J, Pan X, et al. Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection. J Med Virol. 2018;90:1053‐1062. [DOI] [PubMed] [Google Scholar]
107. Li S, Li H, Yang X, et al. Vasorin is a potential serum biomarker and drug target of hepatocarcinoma screened by subtractive‐EMSA‐SELEX to clinic patient serum. Oncotarget. 2015;6:10045‐10059. [DOI] [PMC free article] [PubMed] [Google Scholar]
108. Zhengju XU, Pan X, Wei K, et al. Serum Golgi protein 73 levels and liver pathological grading in cases of chronic hepatitis B. Mol Med Rep. 2015;11:2644‐2652. [DOI] [PMC free article] [PubMed] [Google Scholar]
109. Chen LG, Wang HJ, Yao HB, et al. GP73 is down‐regulated in gastric cancer and associated with tumor differentiation. World J Surg Oncol. 2013;11:132. [DOI] [PMC free article] [PubMed] [Google Scholar]
110. Kristiansen G, Fritzsche FR, Wassermann K, et al. GOLPH2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue‐based diagnostics. Br J Cancer. 2008;99:939‐948. [DOI] [PMC free article] [PubMed] [Google Scholar]
111. Yuen MF, Ng IO, Fan ST, et al. Significance of HBV DNA levels in liver histology of HBeAg and Anti‐HBe positive patients with chronic hepatitis B. Am J Gastroenterol. 2004;99:2032‐2037. [DOI] [PubMed] [Google Scholar]
112. Liu WR, Tian MX, Lei J, et al. High levels of hepatitis b surface antigen are associated with poorer survival and early recurrence of hepatocellular carcinoma in patients with low hepatitis b viral loads. Ann Surg Oncol. 2015;22:843‐850. [DOI] [PubMed] [Google Scholar]
113. Zheng Y, Trivedi T, Lin RC, et al. Loss of the vitamin D receptor in human breast and prostate cancers strongly induces cell apoptosis through downregulation of Wnt/β‐catenin signaling. Bone Res. 2017;5:195‐206. [DOI] [PMC free article] [PubMed] [Google Scholar]
114. Wang F, Long Q, Yu G, et al. Epithelium‐Specific ETS (ESE)‐1 upregulated GP73 expression in hepatocellular carcinoma cells. Cell Biosci. 2014;4:76. [DOI] [PMC free article] [PubMed] [Google Scholar]
115. Wang L, Yao M, Dong Z, et al. Circulating specific biomarkers in diagnosis of hepatocellular carcinoma and its metastasis monitoring. Tumor Biol. 2014;35:9‐20. [DOI] [PMC free article] [PubMed] [Google Scholar]
116. Chen D, Huang C, Ding H, et al. Serum GPC3 combination with AFP diagnostic value for primary liver cancer. Cancer Res 2008;68:12‐16. [Google Scholar]
117. Wright LM, Huster D, Lutsenko S, et al. Hepatocyte GP73 expression in Wilson disease. J Hepatol. 2009;51:557‐564. [DOI] [PMC free article] [PubMed] [Google Scholar]
118. Kiyama N, Abe S, Yamagata S, et al. Evaluation of the biocompatibility of ceramic nanoparticles with A549 lung epithelial cells. Nanosci Nanotech Lett. 2016;8:310‐315. [Google Scholar]
119. Cao Z, Li Z, Wang H, et al. Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection. Liver Int. 2017;37:1612‐1621. [DOI] [PubMed] [Google Scholar]
120. Yang X, Wu F, Chen J, et al. GP73 regulates hepatic steatosis by enhancing SCAP‐SREBPs interaction. Sci Rep 2017;7:714932. [DOI] [PMC free article] [PubMed] [Google Scholar]
121. Xu WJ, Guo BL, Han YG, et al. Diagnostic value of alpha‐fetoprotein‐L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumor Biol. 2014;35:12069‐12074. [DOI] [PubMed] [Google Scholar]
122. Panessawarren BJ, Warren JB, Kisslinger K, et al. Human airway epithelial cell responses to single walled carbon nanotube exposure: nanorope‐residual body formation. Nanosci Nanotech Lett. 2012;4:1110‐1121. [Google Scholar]
123. Wang L, Jang G, Ban DK, et al. Multifunctional stimuli responsive polymer‐gated iron and gold‐embedded silica nano golf balls: nanoshuttles for targeted on‐demand theranostics. Bone Res. 2017;5:17051‐17064. [DOI] [PMC free article] [PubMed] [Google Scholar]
124. Liu T, Yao M, Liu S, et al. Serum Golgi protein 73 is not a suitable diagnostic marker for hepatocellular carcinoma. Oncotarget. 2017;8:16498‐16506. [DOI] [PMC free article] [PubMed] [Google Scholar]
125. Ba MC, Long H, Tang YQ, et al. GP73 expression and its significance in the diagnosis of hepatocellular carcinoma: a review. Int J Clin Exp Pathol. 2012;5:874‐881. [PMC free article] [PubMed] [Google Scholar]
126. Liu Y, Zhang X, Sun T, et al. Knockdown of Golgi phosphoprotein 2 inhibits hepatocellular carcinoma cell proliferation and motility. Oncotarget. 2016;7:21404‐21415. [DOI] [PMC free article] [PubMed] [Google Scholar]
127. Fries E, Gustafsson L, Peterson PA. Four secretory proteins synthesized by hepatocytes are transported from endoplasmic reticulum to Golgi complex at different rates. EMBO J. 1984;3:147‐152. [DOI] [PMC free article] [PubMed] [Google Scholar]
128. Sangiovanni A, Romeo R, Prati GM, et al. Serum expression of lectin reactive alphafetoprotein, des‐gamma‐carboxy prothrombin, Golgi protein‐73 antigen and antibody, for the diagnosis of hepatocellular carcinoma. Hepatology. 2007;46:406A. [Google Scholar]
129. Ying C, Xiao B, Qin Y, et al. GOLPH2‐regulated oncolytic adenovirus, GD55, exerts strong killing effect on human prostate cancer stem‐like cells in vitro and in vivo. Acta Pharmacol Sin. 2017;39:405‐414. [DOI] [PMC free article] [PubMed] [Google Scholar]
130. Witjes CDM, Aalten SMV, Steyerberg EW, et al. Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta‐analysis. Hepatol Int. 2013;7:59‐64. [DOI] [PMC free article] [PubMed] [Google Scholar]
131. Bruix J, Reig M, Sherman M. Evidence‐based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 2016;150:835. [DOI] [PubMed] [Google Scholar]
132. Wang Y, Shan S, Gao Y, et al. Correlation of prognosis with the gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma. J Clin Oncol 2013;31:e15050‐15059. [DOI] [PubMed] [Google Scholar]
133. Shan SG, Gao YT, Xu YJ, et al. Gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma correlates with prognosis of patients. Hepatol Res. 2013;43:1199‐1210. [DOI] [PubMed] [Google Scholar]
134. Hu L, Li L, Xie H, et al. The Golgi localization of GOLPH2 (GP73/GOLM1) is determined by the transmembrane and cytoplamic sequences. PLoS One. 2011;6:e28207. [DOI] [PMC free article] [PubMed] [Google Scholar]
135. Wang J, Cai W, Sun L, et al. Occult HBV infection in peripheral blood neutrophils of chronic hepatitis B and its effects on expression of CXCR1, CXCR2, CXCL8 and CD16. Nanosci Nanotech Lett. 2018;10:244‐251. [Google Scholar]
136. Du J, Hong J, Xu C, et al. Screening and identification of ssDNA aptamer for human GP73. Biomed Res Int. 2015;2015:1‐8. [DOI] [PMC free article] [PubMed] [Google Scholar]
137. Kim HJ, Lv D, Yan Z, et al. Golgi phosphoprotein 2 in physiology and in diseases. Cell Biosci. 2012;2:31‐35. [DOI] [PMC free article] [PubMed] [Google Scholar]
138. Li DJ, Henmi F, Yamagata Y, et al. Clinical evaluation of AFP‐L3: a now tumor marker for aggressive hepatocellular carcinoma. Clin Chem. 2002;48:A19. [Google Scholar]
139. Wu Y, Ma J, Wang Y, et al. Development of an alpha‐fetoprotein and Golgi protein 73 multiplex detection assay using xMAP technology. Clin Chim Acta. 2018;482:209‐214. [DOI] [PubMed] [Google Scholar]
140. Iftikhar R, Kladney RD, Havlioglu N, et al. Disease‐ and cell‐specific expression of GP73 in human liver disease. Am J Gastroenterol. 2004;99:1087‐1095. [DOI] [PubMed] [Google Scholar]
141. Hu L, Yao W, Wang F, et al. GP73 is upregulated by hepatitis c virus (HCV) infection and enhances HCV secretion. PLoS One. 2014;9:e90553‐e90563. [DOI] [PMC free article] [PubMed] [Google Scholar]
142. Song D, Chaerkady R, Tan AC, et al. Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI‐504, in pancreatic cancer. Mol Cancer Ther. 2008;7:3275‐3284. [DOI] [PubMed] [Google Scholar]
143. Sun Y, Zhang J, Li N, et al. Hepatocellular carcinoma xenograft models and biomarkers are powerful tools for the evaluation of the new drugs targeting HCC. Cancer Res. 2011;71:1611. [Google Scholar]
144. Norton PA, Comunale MA, Krakover J, et al. N‐linked glycosylation of the liver cancer biomarker GP73. J Cell Biochem. 2010;104:136‐149. [DOI] [PMC free article] [PubMed] [Google Scholar]
145. Waidely E, Al‐Yuobi AO, Bashammakh AS, et al. Serum protein biomarkers relevant to hepatocellular carcinoma and their detection. Analyst. 2015;141:36‐44. [DOI] [PubMed] [Google Scholar]
146. Lin S, Svoboda KK, Jian QF, et al. The biological function of type I receptors of bone morphogenetic protein in bone. Bone Res. 2016;4:16005‐16013. [DOI] [PMC free article] [PubMed] [Google Scholar]
147. Singhal V, Goh BC, Bouxsein ML, et al. Osteoblast‐restricted disruption of the growth hormone receptor in mice results in sexually dimorphic skeletal phenotypes. Bone Res. 2013;1:85‐97. [DOI] [PMC free article] [PubMed] [Google Scholar]
148. Zhou Y, Li L, Hu L, et al. Golgi phosphoprotein 2 (GOLPH2/GP73/GOLM1) interacts with secretory clusterin. Mol Biol Rep. 2011;38:1457‐1462. [DOI] [PubMed] [Google Scholar]
149. Ali Z, Tang Y, Deng Y, et al. Effect of probe design on chemiluminescence detection of hepatitis B virus and hepatitis C virus. Nanosci Nanotech Lett. 2018;10:127‐134. [Google Scholar]
150. Hann HW, Wang M, Hafner J, et al. Analysis of GP73 in patients with HCC as a function of anti‐cancer treatment. Cancer Biomark. 2010;7:269‐273. [DOI] [PMC free article] [PubMed] [Google Scholar]
151. Wei Z, Ouyang H, Dass CR, et al. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res. 2016;4:15040‐15053. [DOI] [PMC free article] [PubMed] [Google Scholar]
152. Liu M, Li Z, Yang J, et al. Cell‐specific biomarkers and targeted biopharmaceuticals for breast cancer treatment. Cell Prolif. 2016;49:409‐420. [DOI] [PMC free article] [PubMed] [Google Scholar]
153. Pickett JE, Thompson JM, Sadowska A, et al. Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone. Bone Res. 2018;6:13‐20. [DOI] [PMC free article] [PubMed] [Google Scholar]
154. Chen X, Wang Y, Tao J, et al. mTORC1 Up‐regulates GP73 to promote proliferation and migration of hepatocellular carcinoma cells and growth of xenograft tumors in mice. Gastroenterology. 2015;149:741‐752. [DOI] [PubMed] [Google Scholar]
155. Yao S, Zhang J, Chen H, et al. Diagnostic value of immunohistochemical staining of GP73, GPC3, DCP, CD34, CD31, and reticulin staining in hepatocellular carcinoma. J Histochem Cytochem. 2013;61:639‐648. [DOI] [PMC free article] [PubMed] [Google Scholar]
156. Gu Y, Chen W, Zhao Y, et al. Quantitative analysis of elevated serum Golgi protein‐73 expression in patients with liver diseases. Ann Clin Biochem. 2009;46:38‐43. [DOI] [PubMed] [Google Scholar]
157. Ma W, Shao X, Zhao D, et al. Self‐assembled tetrahedral DNA nanostructures promote neural stem cell proliferation and neuronal differentiation. ACS Appl Mater Interfaces. 2018;10:7892‐7900. [DOI] [PubMed] [Google Scholar]
158. Zhang Q, Lin S, Shi S, et al. Anti‐inflammatory and anti‐oxidative effects of tetrahedral DNA nanostructures via the modulation of macrophage responses. ACS Appl Mater Interfaces. 2018;10:3421‐3430. [DOI] [PubMed] [Google Scholar]
159. Xie X, Shao X, Ma W, et al. Overcoming drug‐resistant lung cancer by paclitaxel loaded tetrahedral DNA nanostructures. Nanoscale. 2018;10:5457‐5465. [DOI] [PubMed] [Google Scholar]
160. Yi H, Ur Rehman F, Zhao C, Liu B, He N. Recent advances in nano scaffolds for bone repair. Bone Res. 2016;4:206‐216. [DOI] [PMC free article] [PubMed] [Google Scholar]
161. Shi S, Lin S, Li Y, et al. Effects of tetrahedral DNA nanostructures on autophagy in chondrocytes. Chem Commun (Camb). 2018;54:1327‐1330. [DOI] [PubMed] [Google Scholar]
162. Zhou M, Liu N, Shi S, et al. Effect of tetrahedral DNA nanostructures on proliferation and osteo/odontogenic differentiation of dental pulp stem cells via activation of the notch signaling pathway. Nanomed‐Nanotechnol. 2018;16:S1549‐S9634. [DOI] [PubMed] [Google Scholar]
163. Li Q, Zhao D, Shao X, et al. Aptamer‐modified tetrahedral DNA nanostructure for tumor‐targeted drug delivery. ACS Appl Mater Interfaces. 2017;9:36695‐36701. [DOI] [PubMed] [Google Scholar]
164. Tian T, Zhang T, Zhou T, et al. Synthesis of an ethyleneimine/tetrahedral DNA nanostructure complex and its potential application as a multi‐functional delivery vehicle. Nanoscale. 2017;9:18402‐18412. [DOI] [PubMed] [Google Scholar]
165. Gong T, Xie J, Liao J, et al. Nanomaterials and bone regeneration. Bone Res. 2015;3:123‐129. [DOI] [PMC free article] [PubMed] [Google Scholar]
166. Shi S, Lin S, Shao X, et al. Modulation of chondrocyte motility by tetrahedral DNA nanostructures. Cell Prolif 2017;50:e12368. [DOI] [PMC free article] [PubMed] [Google Scholar]
167. Ibrahim AA, Umar A, Ahmad R, et al. Fabrication and characterization of highly sensitive and selective glucose biosensor based on ZnO decorated carbon nanotubes. Nanosci Nanotech Lett. 2016;8:853‐858. [Google Scholar]
168. Kuzhir P, Ksenevich V, Paddubskaya A, et al. CNT based epoxy resin composites for conductive applications. Nanosci Nanotech Lett. 2016;3:889‐894. [Google Scholar]
169. Ravanan S, Sahayaraj PA, Prema AA. Fabrication and anti‐cancer activity of natural ingredient/extract loaded polycaprolactone (PCL) nanofibres enhanced by plasma treatment. Nanosci Nanotech Lett. 2016;8:348‐354. [Google Scholar]
170. Jeong S, Jang GH, Kim DH. Lignin depolymerization over CuO–MgO–Al₂O₃ mixed oxide catalysts in supercritical ethanol: effect of catalyst preparation methods. Nanosci Nanotech Lett. 2017;9:161‐164. [Google Scholar]
171. Su S, Ling C, Azad F, et al. Fabrication and modification of n‐ZnO/p‐GaN heterojunction light emitting diodes with white light emission characteristics. Nanosci Nanotech Lett. 2017;9:880‐884. [Google Scholar]
172. Wang P, Zhao L, Liu J, et al. Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells. Bone Res. 2014;2:139‐151. [DOI] [PMC free article] [PubMed] [Google Scholar]
173. Xia Y, Li Q, Gong L, et al. Detection of hepatocellular carcinoma biomarker Golgi protein 73 based on magnetic enzyme‐linked immunoassay. J Nanosci Nanotechnol. 2017;17:231‐237. [DOI] [PubMed] [Google Scholar]
174. Lutz H, Pedersen N, Higgins J, et al. Humoral immune reactivity to feline leukemia virus and associated antigens in cats naturally infected with FeLV. Cancer Res. 1980;40:3642‐3651. [PubMed] [Google Scholar]
175. Kladney RD, Tollefson AE, Wold WS, et al. Upregulation of the Golgi protein GP73 by adenovirus infection requires the E1A CtBP interaction domain. Virol. 2002;301:236‐246. [DOI] [PubMed] [Google Scholar]
176. Wei H, Hao X, Li B, et al. GP73 is a potential marker for evaluating AIDS progression and antiretroviral therapy efficacy. Mol Biol Rep. 2013;40:6397‐6405. [DOI] [PubMed] [Google Scholar]
177. Kladney RD, Cui X, Bulla GA, et al. Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease. Hepatology. 2002;35:1431‐1440. [DOI] [PubMed] [Google Scholar]
178. Zhang X, Zhu C, Wang T, et al. GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation. PLoS Pathog. 2017;13:e1006321. [DOI] [PMC free article] [PubMed] [Google Scholar]
179. Zhang Y, Lu J, Dai W, et al. Combination therapy of ursodeoxycholic acid and corticosteroids for primary biliary cirrhosis with features of autoimmune hepatitis: a meta‐analysis. Gastroent Res Pract. 2013;2013:490731. [DOI] [PMC free article] [PubMed] [Google Scholar]
180. Jia Z, Wang L, Liu C, et al. Evaluation of α‐fetoprotein‐L3 and Golgi protein 73 detection in diagnosis of hepatocellular carcinoma. Contemp Oncol. 2014;18:192‐196. [DOI] [PMC free article] [PubMed] [Google Scholar]
181. Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25. [DOI] [PMC free article] [PubMed] [Google Scholar]
182. Hu JS, Wu DW, Liang S, et al. GP73, a resident Golgi glycoprotein, is sensibility and specificity for hepatocellular carcinoma of diagnosis in a hepatitis B‐endemic Asian population. Med Oncol. 2010;27:339‐345. [DOI] [PubMed] [Google Scholar]
183. Block TM, Comunale MA, Lowman M, et al. Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans. Proc Natl Acad Sci USA. 2005;102:779‐784. [DOI] [PMC free article] [PubMed] [Google Scholar]
184. Marrero JA, Romano PR, Nikolaeva O, et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol. 2005;43:1007‐1012. [DOI] [PubMed] [Google Scholar]
185. Yu Y, Gao T, Li H, et al. A novel electrochemical immunosensor for Golgi Protein 73 assay. Electrochem Commun. 2014;42:6‐8. [Google Scholar]
186. Mao Y, Yang H, Xu H, et al. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut. 2010;59:1687‐1693. [DOI] [PubMed] [Google Scholar]
187. Tian L, Wang Y, Xu D, et al. Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases. Int J Cancer. 2011;129:1923‐1931. [DOI] [PubMed] [Google Scholar]
188. Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 2010;73:1907‐1920. [DOI] [PubMed] [Google Scholar]
189. Choi DS, Park JO, Jang SC, et al. Proteomic analysis of microvesicles derived from human colorectal cancer ascites. Proteomics. 2011;11:2745‐2751. [DOI] [PubMed] [Google Scholar]
190. Mathivanan S, Lim JW, Tauro BJ, et al. Proteomics analysis of A33 immunoaffinity‐purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue‐specific protein signature. Mol Cell Proteomics. 2010;9:197‐208. [DOI] [PMC free article] [PubMed] [Google Scholar]
191. Moon PG, Lee JE, You S, et al. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy. Proteomics. 2011;11:2459‐2475. [DOI] [PubMed] [Google Scholar]
192. Liang B, Peng P, Chen S, et al. Characterization and proteomic analysis of ovarian cancer‐derived exosomes. J Proteomics. 2013;80:171‐182. [DOI] [PubMed] [Google Scholar]
193. Kharaziha P, Chioureas D, Rutishauser D, et al. Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel. Oncotarget. 2015;6:21740‐21754. [DOI] [PMC free article] [PubMed] [Google Scholar]
194. Beckler MD, Higginbotham JN, Franklin JL, et al. Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol Cell Proteomics. 2013;12:343‐355. [DOI] [PMC free article] [PubMed] [Google Scholar]
195. Anastasiadou E, Slack FJ. Malicious exosomes. Science. 2014;346:1459‐1460. [DOI] [PubMed] [Google Scholar]
196. Riches A, Campbell E, Borger E, et al. Regulation of exosome release from mammary epithelial and breast cancer cells ‐ a new regulatory pathway. Eur J Cancer. 2014;50:1025‐1034. [DOI] [PubMed] [Google Scholar]
197. Yamashita T, Kamada H, Kanasaki S, et al. Epidermal growth factor receptor localized to exosome membranes as a possible biomarker for lung cancer diagnosis. Pharmazie. 2013;68:969‐973. [PubMed] [Google Scholar]
198. Nilsson J, Skog J, Nordstrand A, et al. Prostate cancer‐derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer. 2009;100:1603‐1607. [DOI] [PMC free article] [PubMed] [Google Scholar]
199. Vlassov AV, Magdaleno S, Setterquist R, et al. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 2012;1820:940‐948. [DOI] [PubMed] [Google Scholar]
200. Yang J, Li J, Dai W, et al. Golgi protein 73 as a biomarker for hepatocellular carcinoma: a diagnostic meta‐analysis. Exp Ther Med. 2015;9:1413‐1420. [DOI] [PMC free article] [PubMed] [Google Scholar]
201. Ying Z, Xin Y, Ying J, et al. Golgi protein 73 versus alpha‐fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta‐analysis. BMC Cancer. 2012;12:17‐24. [DOI] [PMC free article] [PubMed] [Google Scholar]
202. Dai M, Chen X, Liu X, et al. Diagnostic value of the combination of Golgi protein 73 and alpha‐fetoprotein in hepatocellular carcinoma: a meta‐analysis. PLoS One. 2015;10:e0140067‐e0140080. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0001] 1. Xing BY, Qian C, Ying Y, et al. Expression and prognostic significance of Golgi glycoprotein 73 (GP73) with epithelial‐mesenchymal transition (EMT) related molecules in hepatocellular carcinoma (HCC). Diagn Pathol. 2013;8:197‐202. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0002] 2. Xia Y, Han S, Zhu Y, et al. A sensitive three monoclonal antibodies based automatic latex particle‐enhanced turbidimetric immunoassay for Golgi protein 73 detection. Sci Rep. 2017;7:40090‐40099. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0003] 3. Xia Y, Yao A, Xu H, et al. Comparison of two latex nanoparticles with different diameters and the application in detection of biomarker golgi protein 73 in hepatocellular carcinoma. Nanosci Nanotech Lett. 2017;9:398‐405. [Google Scholar]

[cpr12538-bib-0004] 4. Xu WF, Fei YM, Zhou JK, et al. Significance of serum golgi protein 73 (GP73), alpha‐fetoprotein (AFP) and lectin‐reactive alpha‐fetoprotein (AFP‐L3) expression in primary hepatic carcinoma. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2011;25:286‐288. [PubMed] [Google Scholar]

[cpr12538-bib-0005] 5. Yang Y, Liu Q, Zhang H, et al. Silencing of GP73 inhibits invasion and metastasis via suppression of epithelial‐mesenchymal transition in hepatocellular carcinoma. Oncol Rep. 2017;37:1182‐1188. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0006] 6. Donizy P, Kaczorowski M, Biecek P, et al. Golgi‐related proteins GOLPH2 (gp73/golm1) and GOLPH3 (gopp1/midas) in cutaneous melanoma: patterns of expression and prognostic significance. Int J Mol Sci. 2016;17:1619‐1636. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0007] 7. Li XF, Wang GX, Huang TC, et al. Clinical application of gp73 for hepatocellular carcinoma with transarterial chemoembolization combined radiofrequency abolition. Basic Clin Pharmacol Toxicol. 2015;117:2. [Google Scholar]

[cpr12538-bib-0008] 8. Ibrahim GH, Mahmoud MA, Aly NM. Evaluation of circulating transforming growth factor‐beta 1, glypican‐3 and golgi protein‐73 mRNAs expression as predictive markers for hepatocellular carcinoma in Egyptian patients. Mol Biol Rep. 2013;40:7069‐7075. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0009] 9. Weiskirchen R, Tacke F. Combining GP73 with liver stiffness measurements: a proof‐of‐concept for non‐invasive fibrosis assessment in antiviral‐naïve HBV patients. Liver Int. 2017;37:1605‐1607. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0010] 10. Yang HJ, Liu GL, Liu B, et al. GP73 promotes invasion and metastasis of bladder cancer by regulating the epithelial–mesenchymal transition through the TGF‐β1/Smad2 signalling pathway. J Cell Mol Med 2018;22:1650‐1665. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0011] 11. Ye JZ, Yan SM, Yuan CL, et al. GP73 level determines chemotherapeutic resistance in human hepatocellular carcinoma cells. J Cancer. 2018;9:415‐423. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0012] 12. Kawamoto S, Moriwaki K, Nakagawa T, et al. Overexpression of α1,6‐fucosyltransferase in hepatoma enhances expression of Golgi phosphoprotein 2 in a fucosylation‐independent manner. Int J Oncol. 2011;39:203‐208. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0013] 13. Wei H, Li B, Zhang R, et al. Serum GP73, a marker for evaluating progression in patients with chronic HBV infections. PLoS One. 2013;8:e53862‐e53869. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0014] 14. Katada T, Ishiguro H, Kimura M, et al. GP73, contributes to the sensitivity of cisplatin in esophageal cancer. Esophagus. 2009;6:173‐176. [Google Scholar]

[cpr12538-bib-0015] 15. Kai J, Wei L, Zhang Q, et al. GP73 N‐glycosylation at Asn144 reduces hepatocellular carcinoma cell motility and invasiveness. Oncotarget. 2016;7:23530‐23541. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0016] 16. Romano PR, Nikolaeva OV, Steel L, et al. 1261 GP73, a resident golgi membrane protein, appears in sera of patients with viral liver disease and hepatocellular cancer. Hepatology. 2003;38:768. [Google Scholar]

[cpr12538-bib-0017] 17. Almansour M, Sajti L, Melhim W, et al. Ultrastructural hepatic alterations induced by 35 nm zinc oxide nanoparticles. Nanosci Nanotech Lett. 2015;7:763‐769. [Google Scholar]

[cpr12538-bib-0018] 18. Russell WA, Owens JC, Peters DC, et al. Registration of maize germplasm (Reg. Nos. GP72 and GP73). Crop Sci. 1976;16:886. [Google Scholar]

[cpr12538-bib-0019] 19. Kai Z, Zhi D, Jian Z. Biomarkers for hepatocellular carcinoma: progression in early diagnosis, prognosis, and personalized therapy. Biomark Res. 2013;1:10. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0020] 20. Timothy B. The re‐emergence of the GP73 and fucosylated liver cancer biomarkers. Eng Sci. 2014;12:59‐64. [Google Scholar]

[cpr12538-bib-0021] 21. Liu X, Wan X, Lu S, et al. Evaluation of a magnetic particles‐based chemiluminescence enzyme immunoassay for Golgi protein 73 in human serum. Clin Chim Acta. 2015;445:54‐59. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0022] 22. Zhang Y, Xi Y, Fang J, et al. Identification and characterization of monoclonal antibodies against GP73 for use as a potential biomarker in liver cancer screening and diagnosis. J Immunoassay Immunochem. 2016;37:390‐406. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0023] 23. Zhao J, Xu T, Wang F, et al. Mir‐493‐5p suppresses hepatocellular carcinoma cell proliferation through targeting GP73. Biomed Pharmacother. 2017;90:744‐751. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0024] 24. Di J, Tao J, Dan L, et al. Golgi protein 73 activation of MMP‐13 promotes hepatocellular carcinoma cell invasion. Oncotarget. 2015;6:33523‐33533. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0025] 25. Yang H, Xu H, Wang Y, et al. Clinicopathologic correlations of Golgi protein 73 and signal transducer and activator of transcription 3 expression in hepatocellular carcinoma. Transl Cancer Res. 2017;6:238‐246. [Google Scholar]

[cpr12538-bib-0026] 26. Hou X, Yang L, Jiang X, et al. Prognostic significance of golgi protein 73 in hepatocellular carcinoma after hepatectomy in the Chinese population: a meta‐analysis. Int J Clin Exp Med. 2017;10:48‐58. [Google Scholar]

[cpr12538-bib-0027] 27. Zhou N, Wang K, Fang S, et al. Discovery of a potential plasma protein biomarker panel for acute‐on‐chronic liver failure induced by hepatitis B virus. Front Physiol. 2017;8:1009‐1020. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0028] 28. Zhao J, Guo LY, Yang JM, et al. Sublingual vein parameters, AFP, AFP‐L3, and GP73 in patients with hepatocellular carcinoma. Genet Mol Res. 2015;14:7062‐7067. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0029] 29. Shi Y, Chen J, Li L, et al. A study of diagnostic value of golgi protein GP73 and its genetic assay in primary hepatic carcinoma. Technol Cancer Res Treat. 2011;10:287‐294. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0030] 30. Yamamoto K, Imamura H, Matsuyama Y, et al. AFP, AFP‐L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC. J Gastroenterol. 2010;45:1272‐1282. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0031] 31. Zhang YL, Zhang YC, Han W, et al. Effect of GP73 silencing on proliferation and apoptosis in hepatocellular cancer. World J Gastroenterol. 2014;20:11287‐11296. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0032] 32. Yang M, Guan Y, Yang Y, et al. Immunological detection of hepatocellular carcinoma biomarker GP73 based on dissolved magnetic nanoparticles. Colloids Surf A Physicochem Eng Asp. 2014;443:280‐285. [Google Scholar]

[cpr12538-bib-0033] 33. Ozal G, Akbulut H, Akgun N, et al. Golgi protein 73 (gp73) is a useful tumor marker in patients with colon cancer. J Clin Oncol. 2011;29:2696.21606413 [Google Scholar]

[cpr12538-bib-0034] 34. Dong M, Chen ZH, Li X, et al. Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma. Oncol Lett. 2017;14:6277‐6284. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0035] 35. Morota K, Nakagawa M, Sekiya R, et al. A comparative evaluation of Golgi protein‐73, fucosylated hemopexin, α‐fetoprotein, and PIVKA‐II in the serum of patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Clin Chem Lab Med. 2011;49:711‐718. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0036] 36. Yuan Y, Shi L, Wang S. Expression and correlation of CD44 and GP73 in cerebroma tissues. Oncol Lett. 2018;15:4958‐4962. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0037] 37. Yang SL, Zeng C, Fang X, et al. Hepatitis B virus upregulates GP73 expression by activating the HIF‐2α signaling pathway. Oncol Lett. 2018;15:5264‐5270. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0038] 38. Hull C, Regehr AWG. Identification of an inhibitory circuit that regulates cerebellar golgi cell activity. Neuron. 2012;73:149‐158. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0039] 39. Jiang JC, Zhou LF. Advances on Golgi glycoprotein 73 and its association with diseases. J Zhejiang Univ. 2012;41:215‐221. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0040] 40. Wang Y, Yang H, Xu H, et al. Golgi protein 73, not Glypican‐3, may be a tumor marker complementary to α‐Fetoprotein for hepatocellular carcinoma diagnosis. J Gastroenterol Hepatol. 2014;29:597‐602. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0041] 41. Wang F, Li Z, Li L, et al. GP73 was upregulated in PBMC stimulated with ConA but failed to promote lymphocyte proliferation. Cell Biol Int. 2015;39:334‐340. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0042] 42. Castaldo G, Monaco L, Castaldo L, et al. An observational study of sequential protein‐sparing, very low‐calorie ketogenic diet (Oloproteic diet) and hypocaloric Mediterranean‐like diet for the treatment of obesity. Int J Food Sci Nutr. 2016;67:696‐706. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0043] 43. Sai W, Wang L, Zheng W, et al. Abnormal expression of Golgi protein 73 in clinical values and their role in HBV‐related hepatocellular carcinoma diagnosis and prognosis. Hepat Mon. 2015;15:e32918. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0044] 44. Tian SB, Yu JC, Kang WM, et al. Combined detection of CEA, CA 19‐9, CA 242 and CA 50 in the diagnosis and prognosis of resectable gastric cancer. Asian Pac J Cancer Prev. 2014;15:6295‐6300. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0045] 45. Li J, Wang B, Gu S, et al. Amperometric low potential aptasensor for the fucosylated Golgi protein 73, a marker for hepatocellular carcinoma. Microchim Acta. 2017;184:1‐6. [Google Scholar]

[cpr12538-bib-0046] 46. Tunissiolli NM, Castanhole‐Nunes MMU, Biselli‐Chicote PR, et al. Hepatocellular carcinoma: a comprehensive review of biomarkers, clinical aspects, and therapy. Asian Pac J Cancer Prev. 2017;18:863‐872. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0047] 47. Moustafa TA, Aly MM, Abu‐Zahab Z, et al. Evaluation of erythropoietin level in vitreous and serum with detection of erythropoietin gene polymorphism in Egyptian patients with proliferative diabetic retinopathy. Egypt Retina J. 2017;4:71‐76. [Google Scholar]

[cpr12538-bib-0048] 48. Zhang A, Cao B. Brian. Generation and characterization of an anti‐GP73 monoclonal antibody for immunoblotting and sandwich ELISA. J Biomed Mater Res. 2012;26:467‐473. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0049] 49. Li L, Wen L, Gong Y, et al. Xenopus as a model system for the study of GOLPH2/GP73 function: Xenopus GOLPH2 is required for pronephros development. PLoS One. 2012;7:e38939. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0050] 50. Li QW, Chen HB, Li ZY, et al. Preparation and characterization of Anti‐GP73 monoclonal antibodies and development of double‐antibody sandwich ELISA. Asian Pac J Cancer Prev. 2015;16:2043‐2049. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0051] 51. Wang NY, Wang C, Li W, et al. Prognostic value of serum AFP, AFP‐L3, and GP73 in monitoring short‐term treatment response and recurrence of hepatocellular carcinoma after radiofrequency ablation. Asian Pac J Cancer Prev. 2014;15:1539‐1544. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0052] 52. Liu H, Li P, Zhai Y, et al. Diagnostic value of glypican‐3 in serum and liver for primary hepatocellular carcinoma. World J Gastroenterol. 2010;16:4410‐4415. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0053] 53. Kladney RD, Bulla GA, Guo L, et al. GP73, a novel Golgi‐localized protein upregulated by viral infection. Gene. 2000;249:53‐65. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0054] 54. Li J, Cheng ZJ, Liu Y, et al. Serum thioredoxin is a diagnostic marker for hepatocellular carcinoma. Oncotarget. 2015;6:9551‐9563. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0055] 55. He Q, Li JK, Li F, et al. Mechanism of action of gypenosides on type 2 diabetes and non‐alcoholic fatty liver disease in rats. World J Gastroenterol. 2015;21:2058‐2066. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0056] 56. Guan Y, Li A, Xiao W, et al. The efficacy and safety of Endostar combined with chemoradiotherapy for patients with advanced, locally recurrent nasopharyngeal carcinoma. Oncotarget. 2015;6:33926‐33934. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0057] 57. Ni R, Xiao M, Jin F, et al. Clinical value of hepatoma‐specific Alpha‐fetoprotein in the diagnosis of hepatocellular carcinoma. Cancer Bio Med. 2006;3:153‐157. [Google Scholar]

[cpr12538-bib-0058] 58. Jiang K, Li W, Shang S, et al. Aberrant expression of Golgi protein 703 is indicative of a poor outcome in hepatocellular carcinoma. Oncol Rep. 2016;35:2141‐2150. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0059] 59. Lu XL, Liang X, Zhang YX, et al. Saikosaponin D inhibits proliferation and induces apoptosis via C/EBPβ‐p53 signal pathway in human hepatoma HepG2 cells. J Pharm Anal. 2010;22:252‐254. [Google Scholar]

[cpr12538-bib-0060] 60. Jing JS, Ye W, Jiang YK, et al. The value of GPC3 and GP73 in clinical diagnosis of hepatocellular carcinoma. Clin Lab. 2017;63:1903‐1909. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0061] 61. Liu LP, Chen JK, Liu YM, et al. Depletion of GP73 inhibits invasion and metastasis of hepatocellular carcinoma cells. Zhonghua Zhong Liu Za Zhi. 2017;39:497‐501. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0062] 62. Zhang X, Meng S, Zhang R, et al. GP73‐regulated oncolytic adenoviruses possess potent killing effect on human liver cancer stem‐like cells. Oncotarget. 2016;7:29346‐29358. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0063] 63. Cao Z, Li Z, Liu Y, et al. A novel non‐invasive Golgi protein 73 (GP73)‐based model accurately diagnoses significant fibrosis in chronic liver disease. J Hepatol. 2017;66:S677. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0064] 64. Ai N, Liu W, Li ZG, et al. High expression of GP73 in primary hepatocellular carcinoma and its function in the assessment of transcatheter arterial chemoembolization. Oncol Lett. 2017;14:3953‐3958. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0065] 65. Shek FH, Lai TCW, Fatima S, et al. Oncofetal molecules as biomarkers and drug targets for hepatic cancer New Advances on Disease Biomarkers & Molecular Targets in Biomedicine. Totowa, NJ: Humana Press; 2013:57‐74. [Google Scholar]

[cpr12538-bib-0066] 66. Tat TN, Duong DC, Tong HV, et al. Optimisation of quantitative miRNA panels to consolidate the diagnostic surveillance of HBV‐related hepatocellular carcinoma. PLoS One. 2018;13:e0196081. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0067] 67. Kang C, Xu R, Xu F, et al. The value of dynamic combined detection of serum tumor biomarkers in diagnosing primary hepatic carcinoma. Cancer Res Clin. 2014;26:531‐534. [Google Scholar]

[cpr12538-bib-0068] 68. Zhang X, Wang T, Dai X, et al. Golgi protein 73 facilitates the interaction of hepatitis C virus NS5A with apolipoprotein E to promote viral particle secretion. Biochem Biophys Res Commun. 2016;479:683‐689. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0069] 69. Hu GS, Li YQ, Yang YM, et al. High expression of Golgi phosphoprotein‐3 is associated with poor survival in patients with hepatocellular carcinoma. Tumor Biol. 2014;35:8625‐8632. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0070] 70. Mao YL, Yang HY, Xu HF, et al. Significance of Golgi glycoprotein 73, a new tumor marker in diagnosis of hepatocellular carcinoma: a primary study. Zhonghua Yi Xue Za Zhi. 2008;88:948‐951. [PubMed] [Google Scholar]

[cpr12538-bib-0071] 71. Li B, Li B, Guo T, et al. The clinical values of serum markers in the early prediction of hepatocellular carcinoma. Biomed Res Int. 2017;2017:5358615. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0072] 72. Bachert C, Fimmel C, Linstedt AD. Endosomal trafficking and proprotein convertase cleavage of cis Golgi protein GP73 produces marker for hepatocellular carcinoma. Traffic. 2007;8:1415‐1423. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0073] 73. Xia FD, Wang ZL, Chen HX, et al. Differential expression of IQGAP1/2 in hepatocellular carcinoma and its relationship with clinical outcomes. Asian Pac J Cancer Prev. 2014;15:4951‐4956. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0074] 74. Li W, Qi K, Wang Z, et al. Golgi phosphoprotein 3 regulates metastasis of prostate cancer via matrix metalloproteinase 9. Int J Clin Exp Pathol. 2015;8:3691‐3700. [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0075] 75. Donizy P, Biecek P, Halon A, et al. Nucleoli cytomorphology in cutaneous melanoma cells‐a new prognostic approach to an old concept. Diagn Pathol. 2017;12:88‐96. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0076] 76. Xu Z, Liu L, Pan X, et al. Serum Golgi protein 73 (GP73) is a diagnostic and prognostic marker of chronic HBV liver disease. Medicine. 2015;94:e659. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0077] 77. Hou S, Xiao M, Runzhou NI, et al. Serum GP73 is complementary to AFP and GGT‐II for the diagnosis of hepatocellular carcinoma. Oncol Lett. 2013;6:1152‐1158. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0078] 78. Mehta A, Herrera H, Block T. Chapter seven – glycosylation and liver cancer. Adv Cancer Res. 2015;126:257‐279. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0079] 79. Liang R, Chen XY, Ge LY, et al. Meta‐analysis supports the diagnostic value of GP73 in primary liver cancer. Clin Res Hepatol Gastroenterol. 2015;39:71‐72. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0080] 80. Yao M, Wang L, Psc L, et al. The clinical significance of gp73 in immunologically mediated chronic liver diseases: experimental data and literature review. Clin Rev Allergy Immunol. 2017;2017:1‐13. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0081] 81. Zhao Y, Wang M, Cui C, et al. Significance of combined tests of serum golgi glycoprotein 73 and other biomarkers in diagnosis of small primary hepatocellular carcinoma. Cancer Biomark. 2016;15:677‐683. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0082] 82. Huo Q, Zheng Z, Liu J, et al. Diagnosis value of combined detection of serum golgi protein 73, desgamma carboxy prothrombin and α‐fetoprotein in primary hepatic carcinoma. Zhonghua Yi Xue Za Zhi. 2015;95:757‐760. [PubMed] [Google Scholar]

[cpr12538-bib-0083] 83. Cheng J, Wang W, Zhang Y, et al. Prognostic role of pre‐treatment serum AFP‐l3% in hepatocellular carcinoma: systematic review and meta‐analysis. PLoS One. 2014;9:e87011. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0084] 84. Malaguarnera G, Giordano M, Paladina I, et al. Serum markers of hepatocellular carcinoma. Digest Dis Sci. 2010;55:2744‐2755. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0085] 85. Cao Z, Li Z, Wang Y, et al. Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection. J Viral Hepatitis. 2017;24:57‐65. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0086] 86. Yuan L, Zou Z, Bing Z, et al. CXCL10 decreases GP73 expression in hepatoma cells at the early stage of hepatitis c virus (HCV) infection. Int J Mol Sci. 2013;14:24230‐24241. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0087] 87. Wei H, Zhang J, Li H, et al. GP73, a new marker for diagnosing HBV‐ACLF in population with chronic HBV infections. Diagn Micr Infec Dis. 2014;79:19‐24. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0088] 88. Zhou YY, Jiang JC, You J, et al. Effect of Golgi phosphoprotein 2 (GOLPH2/GP73) on autophagy in human hepatocellular carcinoma HepG2 cells. Tumor Biol. 2015;36:3399‐3406. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0089] 89. Zhang ZQ, Meng H, Wang N, et al. Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol. 2014;9:135‐141. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0090] 90. Hu B, Tian X, Sun J, et al. Evaluation of individual and combined applications of serum biomarkers for diagnosis of hepatocellular carcinoma: a meta‐analysis. Int J Mol Sci. 2013;14:23559‐23580. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0091] 91. Chiappini F. Circulating tumor cells measurements in hepatocellular carcinoma. Int J Hepatol. 2012;2012:684802‐684817. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0092] 92. Yong Q, Chen J, Xin L, et al. Serum gp73 is also a biomarker for diagnosing cirrhosis in population with chronic HBV infection. Clin Biochem. 2014;47:216‐222. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0093] 93. Qiao SS, Cui ZQ, Gong L, et al. Simultaneous measurements of serum AFP, GPC‐3 and HCCR for diagnosing hepatocellular carcinoma. Hepatogastroenterology. 2011;58:1718‐1724. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0094] 94. Pillai AA, Fimmel CJ. Emerging serum biomarkers of HCC. Primary Liver Cancer. 2012;2012:247‐262. [Google Scholar]

[cpr12538-bib-0095] 95. Liu G, Zhang Y, He F, et al. Expression of GOLPH2 is associated with the progression of and poor prognosis in gastric cancer. Oncol Rep. 2014;32:2077‐2085. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0096] 96. Arora G, Flores R, Wright L, et al. Abstract 1323: Liver‐specific knockout mice and liver‐derived cell lines provide insights into potential roles for the GP73/GOLM1 HCC serum biomarker ‐ association with sustained cell proliferation. J Cancer Res. 2012;72:1323. [Google Scholar]

[cpr12538-bib-0097] 97. Jiang K, Shang S, Li W, et al. Multiple lectin assays for detecting glyco‐alteration of serum GP73 in liver diseases. Glycoconj J. 2015;32:657‐664. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0098] 98. Ozkan H, Erdal H, Tutkak H, et al. Diagnostic and prognostic validity of Golgi protein 73 in hepatocellular carcinoma. Digestion. 2012;86:83‐88. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0099] 99. Tan LY. Correlation between GP73 protein and human liver disease. Zhonghua Gan Zang Bing Za Zhi. 2007;15:958‐959. [PubMed] [Google Scholar]

[cpr12538-bib-0100] 100. Wang M, Long RE, Comunale MA, et al. Analysis of GP73 in combination with fucosylated alpha‐1‐antitrypsin and fucosylated kininogen as a biomarker of primary hepatocellular carcinoma. Cancer Biomark. 2008;4:155. [Google Scholar]

[cpr12538-bib-0101] 101. Sun S, Day PJ, Lee NP, et al. Biomarkers for early detection of liver cancer: focus on clinical evaluation. Protein Pept Lett. 2009;16:473‐478. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0102] 102. Naryshkina T, Liu J, Florens L, et al. Thermus thermophilus bacteriophage phiYS40 genome and proteomic characterization of virions. J Mol Biol. 2006;364:667‐677. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0103] 103. Fimmel CJ, Wright L. Golgi protein 73 as a biomarker of hepatocellular cancer: development of a quantitative serum assay and expression studies in hepatic and extrahepatic malignancies. Hepatology. 2009;49:1421‐1423. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0104] 104. Wang MJ, Long RE, Comunale MA, et al. Novel fucosylated biomarkers for the early detection of hepatocellular carcinoma. Cancer Epidermiol Biomarkers Prev. 2009;18:1914‐1921. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0105] 105. Andreana L, Isgrò G, Pleguezuelo M, et al. Surveillance and diagnosis of hepatocellular carcinoma in patients with cirrhosis. World J Hepatol. 2009;1:48‐61. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0106] 106. Xu Z, Shen J, Pan X, et al. Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection. J Med Virol. 2018;90:1053‐1062. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0107] 107. Li S, Li H, Yang X, et al. Vasorin is a potential serum biomarker and drug target of hepatocarcinoma screened by subtractive‐EMSA‐SELEX to clinic patient serum. Oncotarget. 2015;6:10045‐10059. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0108] 108. Zhengju XU, Pan X, Wei K, et al. Serum Golgi protein 73 levels and liver pathological grading in cases of chronic hepatitis B. Mol Med Rep. 2015;11:2644‐2652. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0109] 109. Chen LG, Wang HJ, Yao HB, et al. GP73 is down‐regulated in gastric cancer and associated with tumor differentiation. World J Surg Oncol. 2013;11:132. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0110] 110. Kristiansen G, Fritzsche FR, Wassermann K, et al. GOLPH2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue‐based diagnostics. Br J Cancer. 2008;99:939‐948. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0111] 111. Yuen MF, Ng IO, Fan ST, et al. Significance of HBV DNA levels in liver histology of HBeAg and Anti‐HBe positive patients with chronic hepatitis B. Am J Gastroenterol. 2004;99:2032‐2037. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0112] 112. Liu WR, Tian MX, Lei J, et al. High levels of hepatitis b surface antigen are associated with poorer survival and early recurrence of hepatocellular carcinoma in patients with low hepatitis b viral loads. Ann Surg Oncol. 2015;22:843‐850. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0113] 113. Zheng Y, Trivedi T, Lin RC, et al. Loss of the vitamin D receptor in human breast and prostate cancers strongly induces cell apoptosis through downregulation of Wnt/β‐catenin signaling. Bone Res. 2017;5:195‐206. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0114] 114. Wang F, Long Q, Yu G, et al. Epithelium‐Specific ETS (ESE)‐1 upregulated GP73 expression in hepatocellular carcinoma cells. Cell Biosci. 2014;4:76. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0115] 115. Wang L, Yao M, Dong Z, et al. Circulating specific biomarkers in diagnosis of hepatocellular carcinoma and its metastasis monitoring. Tumor Biol. 2014;35:9‐20. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0116] 116. Chen D, Huang C, Ding H, et al. Serum GPC3 combination with AFP diagnostic value for primary liver cancer. Cancer Res 2008;68:12‐16. [Google Scholar]

[cpr12538-bib-0117] 117. Wright LM, Huster D, Lutsenko S, et al. Hepatocyte GP73 expression in Wilson disease. J Hepatol. 2009;51:557‐564. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0118] 118. Kiyama N, Abe S, Yamagata S, et al. Evaluation of the biocompatibility of ceramic nanoparticles with A549 lung epithelial cells. Nanosci Nanotech Lett. 2016;8:310‐315. [Google Scholar]

[cpr12538-bib-0119] 119. Cao Z, Li Z, Wang H, et al. Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection. Liver Int. 2017;37:1612‐1621. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0120] 120. Yang X, Wu F, Chen J, et al. GP73 regulates hepatic steatosis by enhancing SCAP‐SREBPs interaction. Sci Rep 2017;7:714932. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0121] 121. Xu WJ, Guo BL, Han YG, et al. Diagnostic value of alpha‐fetoprotein‐L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumor Biol. 2014;35:12069‐12074. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0122] 122. Panessawarren BJ, Warren JB, Kisslinger K, et al. Human airway epithelial cell responses to single walled carbon nanotube exposure: nanorope‐residual body formation. Nanosci Nanotech Lett. 2012;4:1110‐1121. [Google Scholar]

[cpr12538-bib-0123] 123. Wang L, Jang G, Ban DK, et al. Multifunctional stimuli responsive polymer‐gated iron and gold‐embedded silica nano golf balls: nanoshuttles for targeted on‐demand theranostics. Bone Res. 2017;5:17051‐17064. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0124] 124. Liu T, Yao M, Liu S, et al. Serum Golgi protein 73 is not a suitable diagnostic marker for hepatocellular carcinoma. Oncotarget. 2017;8:16498‐16506. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0125] 125. Ba MC, Long H, Tang YQ, et al. GP73 expression and its significance in the diagnosis of hepatocellular carcinoma: a review. Int J Clin Exp Pathol. 2012;5:874‐881. [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0126] 126. Liu Y, Zhang X, Sun T, et al. Knockdown of Golgi phosphoprotein 2 inhibits hepatocellular carcinoma cell proliferation and motility. Oncotarget. 2016;7:21404‐21415. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0127] 127. Fries E, Gustafsson L, Peterson PA. Four secretory proteins synthesized by hepatocytes are transported from endoplasmic reticulum to Golgi complex at different rates. EMBO J. 1984;3:147‐152. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0128] 128. Sangiovanni A, Romeo R, Prati GM, et al. Serum expression of lectin reactive alphafetoprotein, des‐gamma‐carboxy prothrombin, Golgi protein‐73 antigen and antibody, for the diagnosis of hepatocellular carcinoma. Hepatology. 2007;46:406A. [Google Scholar]

[cpr12538-bib-0129] 129. Ying C, Xiao B, Qin Y, et al. GOLPH2‐regulated oncolytic adenovirus, GD55, exerts strong killing effect on human prostate cancer stem‐like cells in vitro and in vivo. Acta Pharmacol Sin. 2017;39:405‐414. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0130] 130. Witjes CDM, Aalten SMV, Steyerberg EW, et al. Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta‐analysis. Hepatol Int. 2013;7:59‐64. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0131] 131. Bruix J, Reig M, Sherman M. Evidence‐based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 2016;150:835. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0132] 132. Wang Y, Shan S, Gao Y, et al. Correlation of prognosis with the gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma. J Clin Oncol 2013;31:e15050‐15059. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0133] 133. Shan SG, Gao YT, Xu YJ, et al. Gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma correlates with prognosis of patients. Hepatol Res. 2013;43:1199‐1210. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0134] 134. Hu L, Li L, Xie H, et al. The Golgi localization of GOLPH2 (GP73/GOLM1) is determined by the transmembrane and cytoplamic sequences. PLoS One. 2011;6:e28207. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0135] 135. Wang J, Cai W, Sun L, et al. Occult HBV infection in peripheral blood neutrophils of chronic hepatitis B and its effects on expression of CXCR1, CXCR2, CXCL8 and CD16. Nanosci Nanotech Lett. 2018;10:244‐251. [Google Scholar]

[cpr12538-bib-0136] 136. Du J, Hong J, Xu C, et al. Screening and identification of ssDNA aptamer for human GP73. Biomed Res Int. 2015;2015:1‐8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0137] 137. Kim HJ, Lv D, Yan Z, et al. Golgi phosphoprotein 2 in physiology and in diseases. Cell Biosci. 2012;2:31‐35. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0138] 138. Li DJ, Henmi F, Yamagata Y, et al. Clinical evaluation of AFP‐L3: a now tumor marker for aggressive hepatocellular carcinoma. Clin Chem. 2002;48:A19. [Google Scholar]

[cpr12538-bib-0139] 139. Wu Y, Ma J, Wang Y, et al. Development of an alpha‐fetoprotein and Golgi protein 73 multiplex detection assay using xMAP technology. Clin Chim Acta. 2018;482:209‐214. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0140] 140. Iftikhar R, Kladney RD, Havlioglu N, et al. Disease‐ and cell‐specific expression of GP73 in human liver disease. Am J Gastroenterol. 2004;99:1087‐1095. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0141] 141. Hu L, Yao W, Wang F, et al. GP73 is upregulated by hepatitis c virus (HCV) infection and enhances HCV secretion. PLoS One. 2014;9:e90553‐e90563. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0142] 142. Song D, Chaerkady R, Tan AC, et al. Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI‐504, in pancreatic cancer. Mol Cancer Ther. 2008;7:3275‐3284. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0143] 143. Sun Y, Zhang J, Li N, et al. Hepatocellular carcinoma xenograft models and biomarkers are powerful tools for the evaluation of the new drugs targeting HCC. Cancer Res. 2011;71:1611. [Google Scholar]

[cpr12538-bib-0144] 144. Norton PA, Comunale MA, Krakover J, et al. N‐linked glycosylation of the liver cancer biomarker GP73. J Cell Biochem. 2010;104:136‐149. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0145] 145. Waidely E, Al‐Yuobi AO, Bashammakh AS, et al. Serum protein biomarkers relevant to hepatocellular carcinoma and their detection. Analyst. 2015;141:36‐44. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0146] 146. Lin S, Svoboda KK, Jian QF, et al. The biological function of type I receptors of bone morphogenetic protein in bone. Bone Res. 2016;4:16005‐16013. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0147] 147. Singhal V, Goh BC, Bouxsein ML, et al. Osteoblast‐restricted disruption of the growth hormone receptor in mice results in sexually dimorphic skeletal phenotypes. Bone Res. 2013;1:85‐97. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0148] 148. Zhou Y, Li L, Hu L, et al. Golgi phosphoprotein 2 (GOLPH2/GP73/GOLM1) interacts with secretory clusterin. Mol Biol Rep. 2011;38:1457‐1462. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0149] 149. Ali Z, Tang Y, Deng Y, et al. Effect of probe design on chemiluminescence detection of hepatitis B virus and hepatitis C virus. Nanosci Nanotech Lett. 2018;10:127‐134. [Google Scholar]

[cpr12538-bib-0150] 150. Hann HW, Wang M, Hafner J, et al. Analysis of GP73 in patients with HCC as a function of anti‐cancer treatment. Cancer Biomark. 2010;7:269‐273. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0151] 151. Wei Z, Ouyang H, Dass CR, et al. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res. 2016;4:15040‐15053. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0152] 152. Liu M, Li Z, Yang J, et al. Cell‐specific biomarkers and targeted biopharmaceuticals for breast cancer treatment. Cell Prolif. 2016;49:409‐420. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0153] 153. Pickett JE, Thompson JM, Sadowska A, et al. Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone. Bone Res. 2018;6:13‐20. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0154] 154. Chen X, Wang Y, Tao J, et al. mTORC1 Up‐regulates GP73 to promote proliferation and migration of hepatocellular carcinoma cells and growth of xenograft tumors in mice. Gastroenterology. 2015;149:741‐752. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0155] 155. Yao S, Zhang J, Chen H, et al. Diagnostic value of immunohistochemical staining of GP73, GPC3, DCP, CD34, CD31, and reticulin staining in hepatocellular carcinoma. J Histochem Cytochem. 2013;61:639‐648. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0156] 156. Gu Y, Chen W, Zhao Y, et al. Quantitative analysis of elevated serum Golgi protein‐73 expression in patients with liver diseases. Ann Clin Biochem. 2009;46:38‐43. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0157] 157. Ma W, Shao X, Zhao D, et al. Self‐assembled tetrahedral DNA nanostructures promote neural stem cell proliferation and neuronal differentiation. ACS Appl Mater Interfaces. 2018;10:7892‐7900. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0158] 158. Zhang Q, Lin S, Shi S, et al. Anti‐inflammatory and anti‐oxidative effects of tetrahedral DNA nanostructures via the modulation of macrophage responses. ACS Appl Mater Interfaces. 2018;10:3421‐3430. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0159] 159. Xie X, Shao X, Ma W, et al. Overcoming drug‐resistant lung cancer by paclitaxel loaded tetrahedral DNA nanostructures. Nanoscale. 2018;10:5457‐5465. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0160] 160. Yi H, Ur Rehman F, Zhao C, Liu B, He N. Recent advances in nano scaffolds for bone repair. Bone Res. 2016;4:206‐216. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0161] 161. Shi S, Lin S, Li Y, et al. Effects of tetrahedral DNA nanostructures on autophagy in chondrocytes. Chem Commun (Camb). 2018;54:1327‐1330. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0162] 162. Zhou M, Liu N, Shi S, et al. Effect of tetrahedral DNA nanostructures on proliferation and osteo/odontogenic differentiation of dental pulp stem cells via activation of the notch signaling pathway. Nanomed‐Nanotechnol. 2018;16:S1549‐S9634. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0163] 163. Li Q, Zhao D, Shao X, et al. Aptamer‐modified tetrahedral DNA nanostructure for tumor‐targeted drug delivery. ACS Appl Mater Interfaces. 2017;9:36695‐36701. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0164] 164. Tian T, Zhang T, Zhou T, et al. Synthesis of an ethyleneimine/tetrahedral DNA nanostructure complex and its potential application as a multi‐functional delivery vehicle. Nanoscale. 2017;9:18402‐18412. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0165] 165. Gong T, Xie J, Liao J, et al. Nanomaterials and bone regeneration. Bone Res. 2015;3:123‐129. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0166] 166. Shi S, Lin S, Shao X, et al. Modulation of chondrocyte motility by tetrahedral DNA nanostructures. Cell Prolif 2017;50:e12368. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0167] 167. Ibrahim AA, Umar A, Ahmad R, et al. Fabrication and characterization of highly sensitive and selective glucose biosensor based on ZnO decorated carbon nanotubes. Nanosci Nanotech Lett. 2016;8:853‐858. [Google Scholar]

[cpr12538-bib-0168] 168. Kuzhir P, Ksenevich V, Paddubskaya A, et al. CNT based epoxy resin composites for conductive applications. Nanosci Nanotech Lett. 2016;3:889‐894. [Google Scholar]

[cpr12538-bib-0169] 169. Ravanan S, Sahayaraj PA, Prema AA. Fabrication and anti‐cancer activity of natural ingredient/extract loaded polycaprolactone (PCL) nanofibres enhanced by plasma treatment. Nanosci Nanotech Lett. 2016;8:348‐354. [Google Scholar]

[cpr12538-bib-0170] 170. Jeong S, Jang GH, Kim DH. Lignin depolymerization over CuO–MgO–Al₂O₃ mixed oxide catalysts in supercritical ethanol: effect of catalyst preparation methods. Nanosci Nanotech Lett. 2017;9:161‐164. [Google Scholar]

[cpr12538-bib-0171] 171. Su S, Ling C, Azad F, et al. Fabrication and modification of n‐ZnO/p‐GaN heterojunction light emitting diodes with white light emission characteristics. Nanosci Nanotech Lett. 2017;9:880‐884. [Google Scholar]

[cpr12538-bib-0172] 172. Wang P, Zhao L, Liu J, et al. Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells. Bone Res. 2014;2:139‐151. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0173] 173. Xia Y, Li Q, Gong L, et al. Detection of hepatocellular carcinoma biomarker Golgi protein 73 based on magnetic enzyme‐linked immunoassay. J Nanosci Nanotechnol. 2017;17:231‐237. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0174] 174. Lutz H, Pedersen N, Higgins J, et al. Humoral immune reactivity to feline leukemia virus and associated antigens in cats naturally infected with FeLV. Cancer Res. 1980;40:3642‐3651. [PubMed] [Google Scholar]

[cpr12538-bib-0175] 175. Kladney RD, Tollefson AE, Wold WS, et al. Upregulation of the Golgi protein GP73 by adenovirus infection requires the E1A CtBP interaction domain. Virol. 2002;301:236‐246. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0176] 176. Wei H, Hao X, Li B, et al. GP73 is a potential marker for evaluating AIDS progression and antiretroviral therapy efficacy. Mol Biol Rep. 2013;40:6397‐6405. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0177] 177. Kladney RD, Cui X, Bulla GA, et al. Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease. Hepatology. 2002;35:1431‐1440. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0178] 178. Zhang X, Zhu C, Wang T, et al. GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation. PLoS Pathog. 2017;13:e1006321. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0179] 179. Zhang Y, Lu J, Dai W, et al. Combination therapy of ursodeoxycholic acid and corticosteroids for primary biliary cirrhosis with features of autoimmune hepatitis: a meta‐analysis. Gastroent Res Pract. 2013;2013:490731. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0180] 180. Jia Z, Wang L, Liu C, et al. Evaluation of α‐fetoprotein‐L3 and Golgi protein 73 detection in diagnosis of hepatocellular carcinoma. Contemp Oncol. 2014;18:192‐196. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0181] 181. Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0182] 182. Hu JS, Wu DW, Liang S, et al. GP73, a resident Golgi glycoprotein, is sensibility and specificity for hepatocellular carcinoma of diagnosis in a hepatitis B‐endemic Asian population. Med Oncol. 2010;27:339‐345. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0183] 183. Block TM, Comunale MA, Lowman M, et al. Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans. Proc Natl Acad Sci USA. 2005;102:779‐784. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0184] 184. Marrero JA, Romano PR, Nikolaeva O, et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol. 2005;43:1007‐1012. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0185] 185. Yu Y, Gao T, Li H, et al. A novel electrochemical immunosensor for Golgi Protein 73 assay. Electrochem Commun. 2014;42:6‐8. [Google Scholar]

[cpr12538-bib-0186] 186. Mao Y, Yang H, Xu H, et al. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut. 2010;59:1687‐1693. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0187] 187. Tian L, Wang Y, Xu D, et al. Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases. Int J Cancer. 2011;129:1923‐1931. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0188] 188. Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 2010;73:1907‐1920. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0189] 189. Choi DS, Park JO, Jang SC, et al. Proteomic analysis of microvesicles derived from human colorectal cancer ascites. Proteomics. 2011;11:2745‐2751. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0190] 190. Mathivanan S, Lim JW, Tauro BJ, et al. Proteomics analysis of A33 immunoaffinity‐purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue‐specific protein signature. Mol Cell Proteomics. 2010;9:197‐208. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0191] 191. Moon PG, Lee JE, You S, et al. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy. Proteomics. 2011;11:2459‐2475. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0192] 192. Liang B, Peng P, Chen S, et al. Characterization and proteomic analysis of ovarian cancer‐derived exosomes. J Proteomics. 2013;80:171‐182. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0193] 193. Kharaziha P, Chioureas D, Rutishauser D, et al. Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel. Oncotarget. 2015;6:21740‐21754. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0194] 194. Beckler MD, Higginbotham JN, Franklin JL, et al. Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol Cell Proteomics. 2013;12:343‐355. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0195] 195. Anastasiadou E, Slack FJ. Malicious exosomes. Science. 2014;346:1459‐1460. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0196] 196. Riches A, Campbell E, Borger E, et al. Regulation of exosome release from mammary epithelial and breast cancer cells ‐ a new regulatory pathway. Eur J Cancer. 2014;50:1025‐1034. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0197] 197. Yamashita T, Kamada H, Kanasaki S, et al. Epidermal growth factor receptor localized to exosome membranes as a possible biomarker for lung cancer diagnosis. Pharmazie. 2013;68:969‐973. [PubMed] [Google Scholar]

[cpr12538-bib-0198] 198. Nilsson J, Skog J, Nordstrand A, et al. Prostate cancer‐derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer. 2009;100:1603‐1607. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0199] 199. Vlassov AV, Magdaleno S, Setterquist R, et al. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 2012;1820:940‐948. [DOI] [PubMed] [Google Scholar]

[cpr12538-bib-0200] 200. Yang J, Li J, Dai W, et al. Golgi protein 73 as a biomarker for hepatocellular carcinoma: a diagnostic meta‐analysis. Exp Ther Med. 2015;9:1413‐1420. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0201] 201. Ying Z, Xin Y, Ying J, et al. Golgi protein 73 versus alpha‐fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta‐analysis. BMC Cancer. 2012;12:17‐24. [DOI] [PMC free article] [PubMed] [Google Scholar]

[cpr12538-bib-0202] 202. Dai M, Chen X, Liu X, et al. Diagnostic value of the combination of Golgi protein 73 and alpha‐fetoprotein in hepatocellular carcinoma: a meta‐analysis. PLoS One. 2015;10:e0140067‐e0140080. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Golgi protein 73 and its diagnostic value in liver diseases

Yanyan Xia

Yuanying Zhang

Mengjiao Shen

Hongpan Xu

Zhiyang Li

Nongyue He

Abstract

1. INTRODUCTION

2. BASIC OVERVIEW OF GP73

2.1. The discovery of GP73

2.2. Structural features of GP73

Figure 1.

2.3. Expression and distribution of GP73

2.4. Influencing factors for GP73 expression

2.5. Functions of GP73

3. DETECTION METHODS FOR GP73

4. RELATIONSHIP BETWEEN GP73 AND LIVER DISEASES

4.1. Relationship between GP73 and hepatitis

4.2. Relationship between GP73 and cirrhosis

4.3. Relationship between GP73 and liver cancer

Table 1.

Figure 2.

Figure 3.

Table 2.

Figure 4.

Table 3.

5. CHALLENGES AND STRATEGIES

ACKNOWLEDGEMENTS

Contributor Information

REFERENCES

ACTIONS

PERMALINK

RESOURCES

Cite

Add to Collections

PERMALINK

Golgi protein 73 and its diagnostic value in liver diseases

Yanyan Xia

Yuanying Zhang

Mengjiao Shen

Hongpan Xu

Zhiyang Li

Nongyue He

Abstract

1. INTRODUCTION

2. BASIC OVERVIEW OF GP73

2.1. The discovery of GP73

2.2. Structural features of GP73

Figure 1.

2.3. Expression and distribution of GP73

2.4. Influencing factors for GP73 expression

2.5. Functions of GP73

3. DETECTION METHODS FOR GP73

4. RELATIONSHIP BETWEEN GP73 AND LIVER DISEASES

4.1. Relationship between GP73 and hepatitis

4.2. Relationship between GP73 and cirrhosis

4.3. Relationship between GP73 and liver cancer

Table 1.

Figure 2.

Figure 3.

Table 2.

Figure 4.

Table 3.

5. CHALLENGES AND STRATEGIES

ACKNOWLEDGEMENTS

Contributor Information

REFERENCES

ACTIONS

PERMALINK

RESOURCES

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