A comprehensive genome-wide profiling comparison between HBV and HCV infected hepatocellular carcinoma

BMC Med Genomics. 2019 Oct 28;12(1):147. doi: 10.1186/s12920-019-0580-x.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, especially in East Asia. Even with the progress in therapy, 5-year survival rates remain unsatisfied. Chronic infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV) has been epidemiologically associated with HCC and is the major etiology in the East Asian population. The detailed mechanism, especially the changes of DNA methylation and gene expression between the two types of virus-related HCC, and their contributions to the HCC development, metastasis, and recurrence remain largely unknown.

Methods: In this integrated analysis, we characterized genome-scale profiles of HBV and HCV infected HCC by comparing their gene expression pattern, methylation profiles, and copy number variations from the publicly accessible data of The Cancer Genome Atlas Program (TCGA).

Results: The HLA-A, STAT1, and OAS2 genes were highly enriched and up-regulated discovered in the HCV-infected HCC. Hypomethylation but not copy number variations might be the major factor for the up-regulation of these immune-related genes in HCV-infected HCC.

Conclusions: The results indicated the different epigenetic changes of HBV/HCV related hepatocarcinogenesis. The top up-regulated genes in HCV group were significantly clustered in the immune-related and defense response pathways. These findings will help us to understand the pathogenesis of HBV/HCV associated hepatocellular carcinoma.

Keywords: DNA methylation; Gene expression; Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations
  • DNA Methylation
  • Gene Expression
  • HLA-A Antigens / genetics
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / pathology
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Liver Neoplasms / complications
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • STAT1 Transcription Factor / genetics
  • Up-Regulation

Substances

  • HLA-A Antigens
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • OAS2 protein, human
  • 2',5'-Oligoadenylate Synthetase