Identification of hepatitis B virus X gene variants between hepatocellular carcinoma tissues and pericarcinoma liver tissues in Eastern China

Int J Clin Exp Pathol. 2014 Aug 15;7(9):5988-96. eCollection 2014.

Abstract

Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide, especially in Eastern China where HBV infection confirmed as the most important pathological element. HBV X gene, extremely easy to mutate and integrate into hepatocytes, plays a significant role in HBV infection and HCC development. We deduced that mutations of integrated HBx gene make transformation more malignant. The aim of the study was to investigate whether there were different mutation patterns between the HCC tissues and the pericarcinoma liver tissues (PCLT) from patients with HCC in Eastern China.

Methods: HBx genes extracted from 287 HCC tissue samples and 195 PCLT tissue samples were analyzed by sequence alignment and stratified analysis with the matched medical records.

Results: Mutations occurred complicated and changeable in both HCC and PCLT. COOH-terminal truncation is more frequently found in HCC than PCLT (P < 0.05). There is no single site mutation of nucleic acid or amino acid makes distribution discrepancy between HCC and PCLT. Hydrophobic/hydrophilic character of amino acid of site 43, 47, 127, 131, 132 make distribution discrepancy between HCC and PCLT in men when stratified for gender (P < 0.05). Hydrophobic/hydrophilic character of amino acid of site 40 makes distribution discrepancy between HCC and PCLT in both male and female (P < 0.05). Hydrophobic/hydrophilic character of amino acid of site 47 and 127 make significant discrepancy among clinical stage I, II, III (P < 0.05).

Conclusions: During the infection and replication of HBV, HBx mutates to adjust itself to the hepatocyte and increase the carcinogenesis. COOH-terminal truncated HBX may play a stimulative role in HBV-related HCC carcinogenesis as well as hydrophobic/hydrophilic character changes in some specific amino acid sites.

Keywords: Hepatitis B virus; X gene; hepatocellular carcinoma; mutation; pericarcinoma liver tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / pathology
  • Cell Transformation, Viral
  • China / epidemiology
  • DNA Mutational Analysis
  • DNA, Viral / genetics
  • Female
  • Genotype
  • Hepatitis B / diagnosis
  • Hepatitis B / epidemiology
  • Hepatitis B / virology*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / pathogenicity
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Liver / pathology
  • Liver / virology*
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology*
  • Male
  • Mutation*
  • Neoplasm Staging
  • Phenotype
  • Risk Factors
  • Sequence Analysis, Protein
  • Trans-Activators / chemistry
  • Trans-Activators / genetics*
  • Viral Regulatory and Accessory Proteins
  • Virus Replication

Substances

  • DNA, Viral
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein