Detection of aberrant p16INK4A methylation in sera of patients with HCV-related liver diseases: An Egyptian study.

Egypt reports the highest prevalence of HCV worldwide, the molecular mechanisms of acute hepatitis C virus (HCV) infection, end-stage hepatitis (cirrhosis), and hepatocellular carcinoma have been extensively studied, but little is known of the changes in liver gene expression during the early stages of liver fibrosis associated with chronic HCV infection. The p16INK4A tumor suppressor gene frequently displays genetic alteration in HCC tissues. The present study was performed to estimate the frequency of methylated p16INK4A in the sera of patients with Hepatitis C Virus (HCV) related chronic active hepatitis (CAH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), and to evaluate p16INK4A role as a tumor marker of HCC. The sera of 17 CAH, 20 LC patients and 25 HCC patients were examined in this study. The methylation status of p16INK4A was evaluated by methylation-specific PCR of serum samples. Methylated p16INK4A was detected in 47.1% (8/17) of CAH patients, 5% (4/20) of LC patients and in 92% (23/25) of HCC patients. HBV markers were detected in (4/25) all had methylated p16INK4A. No association was demonstrated between p16INK4A methylation and serum AFP level in HCC group. Conclusion: The results of this study indicate that aberrant DNA methylation contribute to hepatocarcinogenesis, it may be an early event during hepatocarcinogenesis. As the status of p16INK4A methylation was not associated with serum AFP level, it may have a complementary role with AFP as a tumor marker of HCC.