Identification of Potential Key Genes for Hepatitis B Virus-Associated Hepatocellular Carcinoma by Bioinformatics Analysis

J Comput Biol. 2019 May;26(5):485-494. doi: 10.1089/cmb.2018.0244. Epub 2019 Mar 12.

Abstract

Hepatitis B virus-associated (HBV(+)) hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer with poor clinical outcomes and treatment options. However, the underlying molecular mechanisms are still poorly understood. To explore potential key genes in the development of HBV(+)HCC, four series of data (GSE14520, GSE94660, GSE25599, and GSE55092) derived from Gene Expression Omnibus database were analyzed. Totally, 84 upregulated and 46 downregulated common differentially expressed genes (DEGs) were discovered. Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that these DEGs were mainly enriched in cell division and DNA replication biological processes, nucleoplasm and microtubule cellular components, protein-binding molecular functions, and cell cycle and DNA replication pathways. Through protein-protein interaction analysis, 10 hub DEGs with the highest degree of connectivity were indicated, including TOP2A, CDC20, MAD2L1, BUB1B, RFC4, CCNB1, CDKN3, CCNB2, TPX2, and FEN1. Kaplan-Meier analysis revealed that high expression of TOP2A and CDC20 was associated with poor overall survival, relapse-free survival, and high serum alpha-fetoprotein level in HBV(+)HCC. In conclusion, TOP2A and CDC20 were two potential key genes for HBV(+)HCC. Their value in the diagnosis and treatment of HBV(+)HCC requires further investigation.

Keywords: hepatitis B virus; hepatocellular carcinoma; hub genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology*
  • Computational Biology
  • Databases, Genetic
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Ontology
  • Gene Regulatory Networks / genetics
  • Hepatitis B / genetics
  • Hepatitis B / virology
  • Hepatitis B virus / pathogenicity*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology*
  • Protein Interaction Maps / genetics
  • Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Proteins