Table 1.
Summary of Descriptive Characteristics of the Included Studies (n = 41)
| Author (year), Country | Localization of Malignant Neoplasia | N Case |
N Controls |
Gender | PCDH | Method Analyse | Conclusions |
|---|---|---|---|---|---|---|---|
| Baranova et al. (2018), Czech Republic | Ovary | 51 | 35 | NI | PCDH17 | Methylation | PCDH17 methylation was detected in almost 70% of group case and gene expression analysis revealed decreased expression in all of the tumor samples in comparison to the control ones. Statistically significant negative correlation was found between methylation and levels of expression suggesting potentially methylation-based silencing. |
| Bing et al. (2018), China | Hepatic | 109 | 109 | F: 51 M: 58 | PCDH10 | Gene expression | PCDH10 expression was lower in tumor tissues than that in adjacent nontumor tissues. Kaplan–Meier curves showed that patients with lower PCDH10 expression had a worse overall survival. Moreover, PCDH10 expression level was associated tumor size, tumor node metastasis stage, smoking status and drinking status. |
| Cao et al. (2018), China | Ovary | 68 | 0 | NI | PCDH8 | Immunohistochemistry and others | Protocaderin-8 can be considered as a tumor suppressor and play a crucial role in the progression of ovarian cancer. |
| Li et al. (2018), China | Hypopharynx | 80 | 80 | F: 2 M: 78 |
PCDH8 | Immunohistochemistry, Methylation and others | PCDH8 may serve as a useful prognostic biomarker and potential therapeutic target for patients with hypopharyngeal carcinoma. |
| Chen et al. (2017), China | Gastric | 119 | 75 | F*: 21 (17.6%)M*: 98 (82.4%) | PCDH7 | Immunohistochemistry and others | Low expression and decreased PCDH7 may promote cell migration and invasion by inhibiting E-cadherin expression. |
| Lin et al. (2017), China | Prostate | 117 | 47 | M: 117 | PCDH8 | Methylation | PCDH8 was methylated in serum samples of case than in controls. This methylation was correlated with advanced clinical stage, higher level of preoperative PSA, and positive lymph node metastasis. Moreover, patients with PCDH8 methylation had worse BCR-free survival than patients without. |
| Lin et al. (2017), China | Kidney | 142 | 34 | F: 45 M: 97 | PCDH17 | Methylation | PCDH17 was more methylated in case than in controls and methylation in serum was correlated with advanced stage, higher grade, lymph node metastasis and tumor progression. In addition, patients with methylated PCDH17 had shorter progression-free survival and overall survival than patients without, and methylation in serum was an independent prognostic factor for worse progression-free survival and overall survival of patients. |
| Wu et al. (2017), China. | Hepatic | 317 | 0 | F: 35 (11%)M: 282 (89%) | PCDH20 | Immunohistochemistry | Decreased expression of protocadherin 20 was observed in patients and was an independent risk factor for mortality. |
| Deng et al. (2016), China | Prostate | 171 | 65 | M*: 236 | PCDH10 | Methylation | PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis and BCR. In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival. The methylation in serum is an independent predictor of worse BCR-free survival and overall survival. |
| Lin et al. (2016), China | Bladder (non invasive muscle) | 199 | 25 | F: 61 (30.7%)M: 138 (69.3%) | PCDH7 | Immunohistochemistry | PCDH7 expression was decreased in invasive non-muscular bladder cancer tissues and low PCDH7 expression was associated with high pathological grade, relapse, and tumor progression. In addition, low expression is an independent prognostic factor for patient outcome. |
| Zhang et al. (2016), China | Hepatic | 50 | 50 | F*: 39 M*: 11 | PCDH8 | Immunohistochemistry and Methylation | PCDH8 is often inactivated by promoter methylation in liver cancer and can serve as a valuable diagnostic biomarker for early detection and for predicting an unfavorable clinical feature. |
| Chen et al. (2015), China | Nasopharyngeal | 51 | 13 | F*: 12 M*: 39 | PCDH20 | Immunohistochemistry, Methylation and others | PCDH20 can inhibit cell proliferation, migration and invasion by antagonizing the Wnt/β-catenin and EMT signaling pathway in nasopharyngeal cancer. |
| Chen et al. (2015), China | Gastric | 1 072 | 0 | F: 315 (29.4%)M: 757 (70.6%) | PCDH9 | Immunohistochemistry, Methylation and others | Decreased expression of PCDH9 is frequent in metastases of human gastric cancer and its expression is an independent prognostic factor. |
| Dang et al. (2015), China | Hepatic | 86 | 78 | F: 22 M: 64 | PCDH17 | Immunohistochemistry and others | PCDH-17 expression was clinically correlated with overall prognosis as well as metas- tasis in vivo and inhibit metastasis via EGFR/MEK/ERK signaling pathway ex vivo. |
| Harada et al. (2015), China | Lung (non-small cells) | 109 | 0 | F: 42 M: 67 | PCDH10 | Immunohistochemistry and Methylation | PCDH10 promoter methylation plays a significant role in the progression of non-small cell lung cancer and may be a promising prognostic marker for patients with curatively resected pathological stage I. |
| Author (year), Country | Localization of Malignant Neoplasia | N Case |
N Controls |
Gender | PCDH | Method Analyse | Conclusions |
| Hou et al. (2015), Japan | Gastric | 471 | 0 | F: 118 (25.1%)M: 353 (74.9%) | PCDH10 | Methylation | Current findings suggest that the count of hypermethylated CpG sites from the PCDH10 DNA promoter to assess the prognosis of gastric cancer.s |
| Lin et al. (2015), China | Prostate | 167 | 44 | M: 211 | PCDH17 | Methylation | PCDH17 methylation was associated with advanced pathological stage, higher Gleason score, high- er preoperative PSA levels, BCR, and shorter BCR-free survival. |
| Lin et al. (2015), China | Kidney | 191 | 191 | F*: 77 (40.3%)M*: 114 (59.7%) | PCDH17 | Methylation | PCDH17 methylation is significantly correlated with advanced stage, higher grade, and lymph node metastasis. Moreover, it is an independent prognostic factor for progression-free survival and overall survival of patients. |
| Lv et al. (2015), China | Hepatic | 107 | 0 | F: 35 M: 72 | PCDH20 | Methylation and others | PCDH20 can inhibit cell proliferation and cell migration, through antagonizing Wnt/b-catenin signalling pathway |
| Deng et al. (2014), China | Gastric | 458 | 25 | F*: 145 (31.6%)M*: 313 (68.34%) | PCDH10 | Methylation and others | Protocadherin-10 promoter methylation was more in case and was associated with poorer survival. |
| Lin et al. (2014), China | Prostate | 152 | 51 | M: 203 | PCDH17 | Methylation | PCDH17 methylation occurred in prostate cancer and was associated with higher pathological Gleason score, advanced pathological stage, higher level of preoperative PSA, positive angiolymphatic invasion, positive lymph node metastasis, and BCR. In addition, methylation was an independent predictor of poor BCR-free survival and overall survival for patients with prostate cancer. |
| Lin et al. (2014), China | Kidney | 153 | 97 | F*: 51 (33.3%)M*: 102 (66.7%) | PCDH8 | Methylation | PCDH8 methylation was more frequent in tumor tissues and was significantly correlated with advanced clinical stage, higher grade , and lymph node metastasis. In addition, methylation was independently associated with poor progression-free survival. |
| Lin et al. (2014), China | Bladder (non invasive muscle) | 233 | 43 | F*: 72 M*: 161 | PCDH8 | Methylation | PCDH8 methylation occurred in tumor tissues and was correlated with advanced stage, high grade, larger tumor size, tumor recurrence and progression. The patients with PCDH8 methylated have shorter recurrence-free survival, progression-free survival and five-year overall survival. |
| Luo et al. (2014), China | Bladder | 151 | 43 | F: 56 M: 138 | PCDH17 | Methylation | PCDH17 promoter methylation was detected in 52.3% of patients with bladder cancer and was associated with larger tumour diameter, high grade and advanced stage. Patients with PCDH17 promoter methylation had significantly shorter overall survival than those with unmethylated PCDH17 promoter. |
| Niu et al. (2014), China | Prostate | 162 | 47 | M: 209 | PCDH8 | Methylation | PCDH8 methylation occurred in tumor tissues and was associated with advanced pathologic stage, higher level of preoperative PSA, higher Gleason score, positive lymph node metastasis, and biochemical recurrence. The patients with methylated have shorter BCR-free survival time. |
| Wang et al. (2014), China | Prostate | 151 | 34 | M: 185 | PCDH10 | Methylation | PCDH10 methylation was more in tumor tissue and was associated with higher preoperative PSA level, higher Gleason Score, advanced clinical stage, lymph node metastasis, angiolymphatic invasion, biochemical recurrence and may be used as an independent predictor of BCR-free survival. |
| Wang et al. (2014), China | Bladder | 115 | 43 | F: 45 M: 113 | PCDH17 | Methylation | Methylation of the PCDH17 promoter was detected in tumor tissueand was associated with high cancer grade, advanced cancer stage, large tumour diameter and tumour recurrence. Methylation was also associated with significantly shorter survival time. |
| Beukers et al. (2013), Netherlands | Bladder | 167 | 35 | F*: 36 (22%)M*: 131 (78%) | PCDH7 | Methylation | PCDH7 showed high methylation ratios in all age categories and could therefore play an important role in early urothelial carcinogenesis. |
| Danese et al. (2013), Italy | Colorectal | 67 | 67** | F: 22 (34.9%)M: 41 (65.1%) | PCDH10 | Methylation | PCDH10 methylation detected in plasma increased with increasing methylation rate in tumor tissues only in early stage cancers, while this correlation was apparently lost in advanced stages. |
| Fang et al. (2013), China | Hepatic | 50 | 50** | F: 16 M: 34 | PCDH10 | Methylation and others | PCDH10 methylation was detected in tumor tissues compared. There were correlations between methylation status of and tumor size, serum AFP levels, metastasis or TNM staging. |
| Lin et al. (2013), China | Bladder | 135 | 34 | F: 49 M: 120 | PCDH8 | Methylation | PCDH8 promoter methylation was detected in tumor tissue and was associated with advanced stage, high grade, tumour recurrence, larger tumour diameter and nonpapillary morphology. In addition, methylation was associated with significantly shorter survival time and was an independent predictor of overall survival. |
| Author (year), Country | Localization of Malignant Neoplasia | N Case |
N Controls |
Gender | PCDH | Method Analyse | Conclusions |
| Ma et al. (2013), China | Bladder | 105 | 33 | F: 38 M: 100 |
PCDH10 | Immunohistochemistry | Downregulated PCDH10 levels correlated with malignant behaviour and poor overall survival in patients with bladder cancer. Downregulated |
| He et al. (2012), China | Nasopharyngeal | 41 | 16 | F: 10 M: 31 |
PCDH8 | Methylation and others | Ectopic expression of PCDH8 in silenced NPC cells significantly inhibited cell colony formation and cell migration. Thus, PCDH8 could be identified as a tumor suppressor in this cancer. |
| Lin et al. (2012), China | Bladder | 117 | 37 | F: 50 M: 104 |
PCDH10 | Methylation | PCDH10 promoter methylation was detected in tumor tissue and was associated with advanced stage, high grade, tumour recurrence and larger tumour size. In addition, methylation was associated with significantly worse survival and was an independent predictor of overall survival. |
| Tang et al. (2012), China | Lung | 40 | 24 | F*: 12 M*: 28 | PCDH10 | Methylation and others | PCDH10 was downregulated in tumor tissues and methylation of was observed % tumor tissues but not in tumor-adjacent or normal tissues. Ectopic expression of PCDH10 in silenced cells can reduce lung cancer cell proliferation and migration. |
| Zhang et al. (2012), China | Gastric | 65 | 10 | F*: 23 M*: 42 | PCDH8 | Methylation and others | PCDH8 methylation was observed in alls cell lines and 55.38% of the primary tumor, but not in normal gastric mucosa, and was associated with lymph node metastasis. |
| Losi et al. (2011), Italy | Colorectal | 28 | 0 | F: 13 M: 15 |
u-PCDH | Immunohistochemistry and others | Down regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis and may therefore play an important role in this pathological process. |
| Haruki et al. (2010), Japan | Esophageal | 145 | 13** | F*: 16 M*: 129 | PCDH17 | Immunohistochemistry, Methylation and others | Silencing of PCDH17 expression through hypermethylation of the promoter or other mechanisms leads to loss of its tumour-suppressive activity. |
| Yu et al. (2010), China | Gastric, Colorectal, Pancreatic | 270 | 270** | NI | PCDH10 | Methylation | PCDH10 methylation was higher in precancerous lesions than in chronic gastritis samples and Kaplan–Meier survival curves showed that PCDH10 methylation was associated signif- icantly with shortened survival in stage I–III gastric cancer patients. |
| Yu et al. (2009), China | Gastric | 104 | 104** | F*: 45 M*: 57 | PCDH10 | Methylation and others | A PCDH10 é um supressor de tumor gástrico; sua metilação nas fases iniciais da carcinogênese gástrica é um fator prognóstico independente. |
| Imoto et al. (2006), Japan | Lung (non-small cells) | 59 | 12 | F: 20 M: 39 |
PCDH20 | Methylation and others | Methylation of this PCDH20 promoter was observed in primary tumor and was associated with a shorter overall survival. Moreover, the PCDH20 methylation status was an independent prognosticato |
* Data entered for control purposes only; **, peri-lesional tissue; NI, not informed; PCDH, Protocadherin; F, female; M, male; PSA, prostate- specific antigen; BCR, biochemical recurrence; CpG, site of cytosine and guanine; AFT, Alpha Fetoprotein; TNM, Classification of Malignant Tumors.