P15 gene methylation in hepatocellular carcinomas: a systematic review and meta-analysis.

OBJECTIVE This study was performed to investigate the correlation between P15 methylation and hepatocellular carcinoma (HCC) and hepatocirrhosis using a meta-analysis of available case control studies. METHODS Previous studies have primarily evaluated the incidence of P15 methylation in HCC and corresponding control groups, and compared the incidence of P15 methylation in liver cirrhosis and control groups. Data regarding publication information, study characteristics, and incidence of P15 methylation in both groups were collected from these studies and summarized. RESULTS Ten studies that assessed P15 gene methylation in 824 HCC tumour tissues and five studies analyzing P15 methylation in 155 liver cirrhosis tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P15 methylation was significantly higher in HCCs than in adjacent non-tumour tissues (OR 9.04, 95% CI 5.80-14.09, P < 0.00001). Moreover, P15 methylation was significantly higher in liver cirrhosis tissues than in control tissues (OR 7.82, 95% CI 3.58-17.07, P < 0.00001). CONCLUSIONS we found that P15 methylation was associated with an increased risk of HCC and liver cirrhosis. P15 hypermethylation induced the inactivation of the P15 gene, which played an important role in hepatocarcinogenesis.