Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages

PLoS One. 2016 Jul 25;11(7):e0158286. doi: 10.1371/journal.pone.0158286. eCollection 2016.

Abstract

Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection.

MeSH terms

  • Adult
  • Biomarkers*
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Chromosome Mapping
  • Cluster Analysis
  • Computational Biology / methods*
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Gene Regulatory Networks
  • Hepatitis B / complications*
  • Hepatitis B / virology
  • Hepatitis B virus*
  • Humans
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Molecular Sequence Annotation
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors

Substances

  • Biomarkers

Grants and funding

This study was supported by the Qing Lan Project of Jiangsu province, and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.