Role of RASSF1A promoter methylation in the pathogenesis of hepatocellular carcinoma: a meta-analysis of 21 cohort studies.

We carried out the current meta-analysis aiming to comprehensively assess the potential role of RASSF1A aberrant promoter methylation in the pathogenesis of hepatocellular carcinoma (HCC). A range of electronic databases were searched: Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966-2013), EMBASE (1980-2013), CINAHL (1982-2013) and the Chinese Biomedical Database (CBM) (1982-2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude risk difference (RD) with their 95% confidence interval (95% CI) was calculated. In the present meta-analysis, 21 clinical cohort studies with a total of 1,205 HCC patients were included. The results of our meta-analysis illustrated that the frequency of RASSF1A promoter methylation in cancer tissues were significantly higher than those of normal, adjacent and benign tissues (cancer tissues vs. normal tissues: RD = 0.63, 95% CI 0.53-0.73, P < 0.001; cancer tissues vs. adjacent tissues: RD = 0.43, 95% CI 0.33-0.53, P < 0.001; cancer tissues vs. benign tissues: RD = 0.48, 95% CI 038-0.58, P < 0.001; respectively). Further subgroup by ethnicity demonstrated that RASSF1A aberrant promoter methylation was correlated with the pathogenesis of HCC among both Asians and Caucasians (all P < 0.05). The current meta-analysis suggests that RASSF1A aberrant promoter methylation may be implicated in the pathogenesis of HCC. Thus, detection of RASSF1A promoter methylation may be a helpful and valuable biomarker for diagnosis and prognosis of HCC.