H3K9me3 enrichment on the p16 promoter was measured by immunoprecipitation-PCR (ChIP-PCR) analyses, and 39 cases of hepatitis B virus (HBV) associated-hepatocellular carcinoma (HCC) and corresponding noncancerous liver tissues were also examined.
The hypermethylation frequency of GSTP1 and RASSF1A showed significant difference between HCCs and liver cirrhosis with or without HBV infection (P<0.05), but differences of the hypermethylation status of APC, E-cadherin, and P16 were not statistically significant.
Generally, these results indicate that persistent HBV infection may be associated with high rate of p16 methylation, and involved in development of HCC through this way.
In addition, p16 methylation status of five cell lines with or without HBV infection was examined to test whether the high frequency of hypermethylation is related to HBV infection.
Our results suggest that methylation of the p16 promoter and the resulting loss of p16 protein expression are early events in a subset of hepatocarcinogenesis and that their detection is useful in the follow up of patients with a high risk of developing HCC, such as those with hepatitis B or C viral infections.