Identification of genes in hepatocellular carcinoma induced by non-alcoholic fatty liver disease

Cancer Biomark. 2020;29(1):69-78. doi: 10.3233/CBM-190169.

Abstract

Background: Hepatocellular carcinoma (HCC) is the leading cause of mortality worldwide. In recent years, the incidence of HCC induced by NAFLD is growing rapidly.

Objective: To screen for new pathogenic genes and related pathways both in NAFLD and HCC, and to explore the pathogenesis of progression from NAFLD to HCC.

Methods: Gene expression microarrays (GSE74656, GSE62232) were used for identifying differentially expressed genes (DEGs). Functional enrichment and pathway enrichment analyses indicated that these DEGs were related to cell cycle and extracellular exosome, which were closely related to NAFLD and HCC development. We then used the Search Tool for the Retrieval of Interacting Genes (STRING) to establish the protein-protein interaction (PPI) network and visualized them in Cytoscape. And the overall survival (OS) analysis and gene expression validation in TCGA of hub genes was performed.

Results: Seven hub genes, including CDK1, HSP90AA1, MAD2L1, PRKCD, ITGB3BP, CEP192, and RHOB were identified. Finally, we verified the expression level of ITGB3BP and CEP192 by quantitative real-time PCR in vitro.

Conclusions: The present study implied possible DEGs, especially the new gene CEP192, in the progression of NAFLD developing to HCC. Further rigorous experiments are required to verify the above results.

Keywords: CEP192; Expression; bioinformatics; hepatocellular carcinoma; non-alcoholic fatty liver disease.

MeSH terms

  • Biomarkers, Tumor / genetics
  • CDC2 Protein Kinase / genetics
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Chromosomal Proteins, Non-Histone / genetics*
  • Computational Biology
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Regulatory Networks / genetics
  • HSP90 Heat-Shock Proteins / genetics
  • Humans
  • Liver Neoplasms / etiology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Mad2 Proteins / genetics
  • Male
  • Microarray Analysis
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Nuclear Proteins / genetics*
  • Protein Interaction Maps
  • Protein Kinase C-delta / genetics
  • rhoB GTP-Binding Protein / genetics

Substances

  • Biomarkers, Tumor
  • Cep192 protein, human
  • Chromosomal Proteins, Non-Histone
  • HSP90 Heat-Shock Proteins
  • HSP90AA1 protein, human
  • ITGB3BP protein, human
  • MAD2L1 protein, human
  • Mad2 Proteins
  • Nuclear Proteins
  • RHOB protein, human
  • PRKCD protein, human
  • Protein Kinase C-delta
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • rhoB GTP-Binding Protein