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. 2018 Apr 21;35(2):139–160. doi: 10.1007/s10719-018-9820-0

Table 1.

Summary of serum overall sialylation changes (TSA, LSA, bound sialic acid, TSA/TP and bound sialic acid/TP) in various cancers. The columns include (1) cancer types, (2) cohort size, (3) methods used for the detection of sialylation changes, (4) major findings for each study, (5) the trend of the sialylation changes and (6) the references for each study; FSA = free sialic acid; HPLC = high performance liquid chromatography; LSA = lipid-bound sialic acid; TP = total protein; TSA = total sialic acid

Malignancy Cohort Size Methods Major findings Effect in the cancer Ref No.
Laryngeal cancer Laryngeal cancer(n = 35); Healthy controls (n = 34) Serum TSA and free sialic acid: thiobarbituric acid method; Serum bound sialic acid: determined as the difference between TSA and FSA; α-1-acid glycoprotein: nephelometric method Higher levels of serum bound sialic acid and α-1-acid glycoprotein, but not free sialic acid, have correlation with the stage of the cancer Serum sialic acid and α-1-acid glycoprotein increased in laryngeal cancer 30
Oral cancer Oral cancer (n = 130); Precancerous conditions (n = 75); Healthy controls (n = 100) Serum and tissue TSA: spectrophotometric method; sialyltransferase activity and sialoproteins: linkage-specific lectins Usefulness of serum and tissue TSA and linkage-specific sialoproteins and sialyltransferase as biomarker in early detection, prognostication and treatment monitoring of oral cancer Serum and tissue sialic acid and linkage-specific sialoproteins and sialyltransferase increased in oral cancer 50
Oral pre-cancer Oral cancer (n = 25); Precancerous conditions (n = 50); Healthy controls (n = 25) Serum TSA and LSA: spectrophotometric method Serum TSA and LSA positively correlated with grades of dysplasia of oral pre-cancer and cancer; LSA showed great potential of clinical utility in indicating premalignant change Serum TSA and LSA increased in oral pre-cancer and cancer 51
Oral pre-cancer Oral cancer (n = 30); Precancerous conditions (n = 30); Healthy controls (n = 30) Serum TSA: resorcinol reagent method Usefulness of serum TSA in monitoring early changes of oral cancer; Positive correlation of serum TSA with stage and tumor burden Serum TSA increased in oral pre-cancer and cancer 52
Oral pre-cancer Oral cancer (n = 25); Precancerous conditions (n = 25); Healthy controls (n = 25) Serum TSA: spectrophotometric method Increased serum TSA has potential utility in initial diagnosis of leukoplakia and squamous cell oral cancer Serum TSA increased in oral pre-cancer and cancer 53
Oral pre-cancer Oral cancer (n = 25); Precancerous conditions (n = 25); Healthy controls (n = 25) Serum TSA: spectrophotometric method Serum TSA has potential utility in early detection of oral cancer Serum TSA increased in oral pre-cancer and cancer 54
Oral pre-cancer Oral cancer (n = 100); Precancerous conditions (n = 50); Healthy controls (n = 100) Serum TSA: spectrophotometric method Serum and salivary TSA/TP showed usefulness in monitoring early changes during oral cancer transformation Serum TSA/TP increased in oral pre-cancer and cancer 55
Oral pre-cancer Oral cancer (n = 41); Precancerous conditions (n = 20); Healthy controls (n = 20) Serum TSA and LSA: spectrophotometric method Potential utility of serum TSA and LSA in oral cancer diagnosis; Serum TSA and LSA positively correlated with clinical stage of the malignancy Serum TSA and LSA increased in oral pre-cancer and cancer 56
Oral pre-cancer Oral leukoplakia (n = 30); Healthy controls (n = 30) Serum TSA and LSA: spectrophotometric method Grades of epithelial dysplasia of oral leukoplakia positively correlated with serum TSA levels, which can serve as markers for the malignant transformation in oral leukoplakia Serum TSA and LSA increased in oral pre-cancer 57
Cholangiocarcinoma Cholangiocarcinoma (n = 89); Benign hepatobiliary diseases (n = 38); Healthy controls (n = 43) Serum TSA: spectrophotometric method Serum TSA has high adjunct diagnostic values for discriminating cholangiocarcinoma, benign hepatobiliary diseases and healthy controls Serum TSA have an increasing trend from controls, benign to cancer 59
Cervical cancer Cervical cancer (n = 108); Healthy controls (n = 125) Serum TSA and LSA: spectrophotometric method Serum TSA and LSA have diagnostic and treatment monitoring value in cervical cancer Serum TSA and LSA increased in cervical cancer 60
Leukemia Leukemia patients (n = 145); Anemia patients (n = 77); Healthy controls (n = 150) Serum TSA/TP and LSA: spectrophotometric method Usefulness of evaluated serum TSA/TP and LSA are useful in diagnosis and treatment monitoring of leukemia Serum TSA/TP and LSA increased in leukemia patients and anemia patients 61
Colorectal cancer Patients (n = 177; 109 patients with colon and 68 patients with rectal); Healthy controls (n = 50) Serum TSA and LSA: spectrophotometric method Serum TSA is sensitive marker and has potential utility in the earliest diagnosis of colorectal, it also play important roles in cancer progression Serum TSA, but not LSA, significantly increased in the cancer group 62
Lung cancer Lung cancer (n = 12); Chronic obstructive lung disease (n = 6); Controls (n = 64; no neoplastic disease) Serum sialic acid: thiobarbituric acid methods Elevated serum sialic acid showed usefulness as a cancer biomarker in lung cancer Serum sialic acid elevated in lung cancer 65
Colorectal cancer Colorectal cancer (n = 30); Healthy controls (n = 810) TSA and free sialic acid: thiobarbituric acid method; Bound sialic acid: determined as the difference between TSA and FSA Serum TSA/TP and bound sialic acid/TP have positive correlation with tumor stage; Serum and tissue bound sialic acid have no correlation Serum TSA, bound sialic acid,TSA/TP and bound sialic acid/TP were significantly higher in cancer; tissue TSA/TP and bound sialic acid/TP were significantly decreased 63
Breast cancer Breast cancer (n = 65); Controls (n = 56) Serum sialic acid: spectrophotometric method Serum sialic acid correlated with tumor stage; Serum sialic acid have no correlation with CEA values Serum sialic acid elevated in breast cancer 64
Endometrial cancer Cancer (n = 52); Healthy controls (n = 20) Serum and tissue sialic acid: spectrophotometric method Serum TSA positively correlated with tumor stages; Tissue sialic acid had no correlation with cancer stages Serum TSA significantly increased in cancer 77
Several types of cancer Breast cancer (N = 54); Lung cancer (n = 17); Colon cancer (n = 15); Ovarian cancer (n = 7); Prostate cancer (n = 5); Leukemia (n = 4); Gastrointestinal cancer (n = 4); Thyroid cancer (n = 3); Pancreatic cancer (n = 3); Adrenal cancer (n = 2); Patients with non-malignant diseases (n = 16); Healthy controls (n = 50) Plasma LSA: spectrophotometric method Plasma LSA showed potential utility as a prognostic marker in a variety of neoplastic conditions with high sensitivity Plasma LSA elevated in a variety of types of cancer 66
Several types of cancer Healthy controls (n = 30); Cancer (n = 78; including patients of stomach, breast, colorectal region and gall bladder cancer) Serum TSA and LSA: spectrophotometric method Serum TSA, TSA/TP positively correlated with metastasis; TSA and TSA/TP are sensitive markers for detection of malignancy and evaluating the efficacy of therapies Serum TSA and TSA/TP significantly raised and serum TP decreased in these types of cancer 67
Stomach cancer Cancer (n = 48); Healthy controls (n = 20) Serum TSA and LSA: spectrophotometric method Serum TSA and LSA showed potentials as indicators of poor or good prognosis Serum TSA and LSA of cancer before therapy were higher than control and that after receiving therapy 68
Thyroid cancer First part: Cancer (n = 50); Healthy controls (n = 20); Second part: Cancer (n = 11); Adenomatous hyperplasia(n = 8; as control) Serum and tissue TSA: thiobarbituric acid methods Usefulness of sialic acid in follow-up and therapeutic response evaluation Serum and tissue sialic acid levels in various types of thyroid cancer were significantly higher than in controls 69
Colorectal cancer Colorectal cancer (n = 97); Acute and chronic disorders (n = 69); Benign colorectal polyps (n = 17); Healthy controls (n = 195) Serum TSA: HPLC; LSA: resorcinol procedure Serum TSA and LSA correlated with the extent of metastasis; TSA and LSA had strong correlation; TSA and LSA showed potential as supplemental markers for staging and monitoring cancer Serum TSA elevated in 32% nonmalignant disorders, 28% localized cancer, and 87% of metastatic cancer 70
Colorectal cancer Colorectal cancer (n = 146); gastrointestinal disease (n = 73); Normal controls (n = 96) Serum TSA: spectrophotometric method Usefulness of serum TSA/TP in colorectal cancer monitoring Serum TSA/TP have an increasing trend from normal controls, pathologic controls to cancer 71
Breast cancer Primary operable breast cancer (n = 64); Recurrent metastatic breast cancer (n = 61); Benign breast disease (n = 106); Normal controls (n = 78) Serum LSA: spectrophotometric method Usefulness of serum LSA in evaluating disease progression, prognosis and identifying resistance to therapy LSA levels greater than cutoff were not seen in normal subjects; presented in 13% benign breast disease, 47% primary breast cancer and 62% recurrent metastatic breast cancer 72
Malignant melanoma Melanoma (n = 50); Healthy controls (n = 40) Serum TSA: enzymatic method Serum TSA can discriminate cancer and healthy controls; More useful for staging and prognosis Serum TSA increased in cancer 73
Malignant melanoma Melanoma (n = 25); Healthy controls (n = 30) Serum sialic acid: thiobarbituric acid method Increased serum sialic acid correlated with tumor burden due to therapy or recurrence Serum sialic acids were significantly elevated in the melanoma 74
Malignant melanoma Melanoma (n = 66); Healthy controls (n = 66); Rheumatoid arthritis (n = 20) Serum-bound sialic acid: thiobarbituric acid method; Serum sialyltransferase: cytidine 5′-monophosphate-N-[4-14C]acetylneuraminic acid incorporation in desialylated fetuin Serum sialic acid showed higher value for monitoring recurrence of cancer than sialyltransferase; Sialic acid and sialyltransferase had correlation Serum bound sialic acid and sialyltransferase were higher in rheumatoid arthritis patients; Serum sialic acid increased in cancer of different stages 75
Cervical cancer Cervical cancer (n = 88); Benign uterine or ovarian disease (n = 44); Healthy controls (n = 26) Serum TSA and LSA: spectrophotometric method Serum TSA or LSA showed no value for early detection or as complemental marker for clinical staging Serum TSA and LSA increased in advanced stage of cancer 82