Involvement of c-myc-regulated genes in hepatocellular carcinoma related to genotype-C hepatitis B virus

J Cancer Res Clin Oncol. 2006 Jul;132(7):473-81. doi: 10.1007/s00432-006-0094-8. Epub 2006 Apr 25.

Abstract

Purpose: The purpose of this study was to elucidate the molecular basis of hepatocellular carcinoma (HCC) caused by genotype-C hepatitis B virus (HBV).

Methods: We compared molecular profiles of 15 HCCs and five non-tumorous livers, all of which were associated with genotype-C HBV infection, using DNA microarray technology.

Results: Our supervised learning identified 237 genes whose expression differed between HCCs and non-tumorous livers. This result was validated by a false discovery rate of 0%. Levels of expression of 35 and 202 genes were higher and lower, respectively, in HCCs than in non-tumorous livers. Among the 237 genes, we highlighted the top 35 upregulated and top 35 down regulated genes in tumor. Interestingly, when overlapping genes were excluded, 12 (e.g., NM23-H2, MCM7, PARP1, YWHAH, HSPB1, and MSH2) of the top 34 upregulated genes and five (e.g., MT1A and MT3) of the top 33 downregulated genes were c-myc-regulated genes. The microarray data for five randomly selected genes (MCM7, UBE2L3, PPIA, CXCL12, and ASS) were confirmed by quantitative real-time reverse transcription-polymerase chain reaction.

Conclusions: Our results indicate that many c-myc-regulated genes are involved in genotype-C-HBV-related HCC, suggesting that c-myc is related to the hepatocarcinogenic activity of genotype-C HBV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology*
  • Down-Regulation
  • Genes, myc*
  • Genotype
  • Hepatitis B virus* / genetics
  • Hepatitis B virus* / isolation & purification
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology*
  • Reverse Transcriptase Polymerase Chain Reaction