DNA methylation changes in normal liver tissues and hepatocellular carcinoma with different viral infection

Abstract

Hepatocellular carcinoma (HCC) is known to be associated with both HBV and HCV. While epigenetic changes have been previously reported to be associated with hepatocellular carcinoma (HCC), whether the epigenetic profile of HBC associated HCC differs from that of HCV-associated HCC is unclear. We analyzed DNA methylation of ten genes (APC, CCND2, CDKN2A, GSTP1, HOXA9, RARB, RASSF1, RUNX, SFRP1, and TWIST1) using MethyLight assays on 65 archived liver tissue blocks. Three genes (APC, CCND2, and GSTP1) were frequently methylated in normal liver tissues. Five genes (APC, CDKN2A, HOXA9, RASSF1, and RUNX) were significantly more frequently methylated in malignant liver tissues than normal liver tissues. Among HCC cases, HOXA9, RASSF1 and SFRP1 were methylated more frequently in HBV-positive HCC cases, while CDKN2A were significantly more frequently methylated in HCV-positive HCC cases. Our data support the hypothesis that HCC resulting from different viral etiologies is associated with different epigenetic changes.

Figure 1

Representative MethyLight amplification curves for CDKN2A, RASSF1, HOXA9, and CCND2. CDKN2A was preferentially methylated in HCV-positive HCCs, while RASSF1 was preferentially methylated in HBV-positive HCCs. Methylation of HOXA9 was HCC specific, and methylation of CCND2 was present in both normal and HCC liver tissues.