Meta-analysis of possible role of cadherin gene methylation in evolution and prognosis of hepatocellular carcinoma with a PRISMA guideline

Abstract

Background: Cadherins (CDHs) have been reported to be associated with cancer. However, the clinical significance of CDH gene methylation in hepatocellular carcinoma (HCC) remains unclear.

Methods: Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, available studies were identified from online electronic database. The overall odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were calculated and analyzed.

Results: A total of 29 eligible studies with 2562 HCC samples and 1685 controls were included. E-cadherin (CDH1) hypermethylation was observed to be significantly higher in HCC than in benign, adjacent, or normal samples. Moreover, CDH1 hypermethylation was not associated with gender, tumor grade, clinical stage, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection in HCC patients. H-cadherin (CDH13), protocadherin-10 (PCDH10), P-cadherin (CDH3), and M-cadherin (CDH15) methylation may have an increased risk of HCC in fewer than 4 studies, and methylated cadherin 8, type 2 (CDH8) and OB-cadherin (CDH11) had a similar OR in HCC and adjacent samples. When HCC samples were compared with normal samples, the analysis of sample type revealed a significantly higher OR in normal blood samples than in normal tissues for hypermethylated CDH1 (50.82 vs 4.44).

Conclusion: CDH1 hypermethylation may play a key role in the carcinogenesis of HCC. However, CDH1 hypermethylation was not correlated with clinicopathological features. Methylated CDH13, PCDH10, CDH3, and CDH15, but not methylated CDH8 or CDH11, may lead to an increased risk of HCC. Hypermethylated CDH1 may become a noninvasive blood biomarker. Further studies with more data are necessary.

Figure 1

Flow chart of the literature search strategy.

Figure 2

Forest plot for the correlation of CDH1 hypermethylation status from 12 publications showing the pooled OR under a random-effects model in 594 HCC versus 581 benign samples, OR = 3.40, 95% CI = 1.35 to 8.59. CDH1 = E-cadherin, CI = confidence interval, HCC = hepatocellular carcinoma, OR = odds ratio.

Figure 3

Forest plot for the association of CDH1 hypermethylation status from 12 studies showing the pooled OR under a random-effects model in 598 HCC versus 471 adjacent samples, OR = 2.42, 95% CI = 1.01 to 5.83. CDH1 = E-cadherin, CI = confidence interval, HCC = hepatocellular carcinoma, OR = odds ratio.

Figure 4

Forest plot for the relationship of CDH1 hypermethylation status from 9 studies showing the pooled OR under a random-effects model in 494 HCC versus 166 normal samples, OR = 7.17, 95% CI = 2.80 to 18.35. CDH1 = E-cadherin, CI = confidence interval, HCC = hepatocellular carcinoma, OR = odds ratio.