CDKN2A promoter methylation and hepatocellular carcinoma risk: A meta-analysis.

AIM: Lots of studies have explored cyclin-dependent kinase inhibitor 2A (CDKN2A) promoter methylation in hepatocellular carcinoma (HCC), but the established results were controversial. Hence, we conducted the meta-analysis to comprehensively investigate the association between CDKN2A promoter methylation and HCC risk.

METHODS: A comprehensive search was implemented through searching PubMed, Web of Science and Embase. Associations of CDKN2A promoter methylation with HCC risk, clinicopathological features, and CDKN2A expression were assessed by the pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Subgroup analyses and meta-regression were served for exploring the potential sources of heterogeneity.

RESULTS: A total of 59 articles including 3067 cases and 2951 controls were incorporated in this meta-analysis. Overall, we observed a high CDKN2A promoter methylation rate (58.18%) in HCC and a significant association between the methylation and HCC risk (OR, 7.07; 95% CI, 5.67-8.80). Furthermore, CDKN2A promoter methylation was robustly associated with decreased mRNA (OR, 13.89; 95% CI, 5.44-35.45) and protein (OR, 48.19; 95% CI, 5.56-417.29). In addition, we found the methylation was related with HBV infection (OR, 3.31; 95% CI, 1.47-7.47), HCV infection (OR, 2.76; 95% CI, 1.80-4.23), cirrhosis status (OR, 1.57; 95% CI, 1.01-2.44) and older age (OR, 1.83; 95% CI, 1.14-2.94).

CONCLUSIONS: Our results indicated that CDKN2A promoter methylation was associated with an enhancive HCC risk and played a crucial role in the process of HCC with a potential value to being a triage marker for HCC.