RASSF1A promoter hypermethylation as a prognostic marker for hepatocellular carcinoma.

This study was performed to determine whether epigenetic aberrant methylation of RASSF1A might be associated with hepatocarcinogenesis. Methylation specific-PCR was performed to identify RASSF1A promoter hypermethylation in 29 tumors and corresponding normal liver tissues. In addition, RASSF1A mRNA levels were analyzed by quantitative real-time reverse transcription-PCR. Aberrant methylation of RASSF1A was detected in 25 of 29 cases (86%), with loss of RASSF1A expression evident in 8 of 22 cases (36%). No correlation between loss of RASSF1A mRNA and promoter hypermethylation of the RASSF1A gene was observed. There was a significant correlation between the methylation status of RASSF1A and hepatocellular carcinoma (HCC) patients who did not undergo chemotherapy (P = 0.03). Multivariate analysis, adjusted for tumor size, treatment, RASSF1A hypermethylation, and RASSF1A under-expression, showed RASSF1A hypermethylation to be assocaited with a better prognosis for HCC patients (HR= 0.089, 95%CI = 0.013-0.578; P = 0.012). Our findings showed that RASSF1A promoter hypermethylation occurs frequently, and may serve as a good prognostic factor.