Comparative analysis of epigenetic and gene expression endpoints between tumorous and non-tumorous tissues from HCV-positive patients with hepatocellular carcinoma.

摘要

Transcriptional silencing induced by promoter CpG island hypermethylation is an important epigenetic mechanism of hepatocarcinogenesis. The goals of our study were to examine promoter methylation and mRNA levels of candidate genes, as well as global changes in DNA methylation, in a cohort of HCV-positive HCC patients from Japan. Methylation-specific PCR was used to assess the methylation status of seven cancer-related genes, while the methylation status of long interspersed nuclear elements was used as marker of global genomic methylation, in tissues obtained from patients who underwent tumor resection surgery. Methylation frequencies for most of the genes were significantly higher in tumorous versus non-tumorous tissues. The methylation status of only three genes correlated with reduced mRNA levels. Genomic DNA was significantly more hypomethylated in tumorous tissues, and was associated with shorter recurrence but not with clinicopathological variables. In summary, this study establishes an aberrant gene-specific and global methylation profile in HCV-associated HCCs.