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Identification of key genes and carcinogenic pathways in hepatitis B virus-associated hepatocellular carcinoma through bioinformatics analysis

  • Sang-Hoon Kim (Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Shin Hwang (Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Gi-Won Song (Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Dong-Hwan Jung (Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Deok-Bog Moon (Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jae Do Yang (Department of Surgery, Jeonbuk National University Hospital) ;
  • Hee Chul Yu (Department of Surgery, Jeonbuk National University Hospital)
  • Received : 2021.07.16
  • Accepted : 2021.09.02
  • Published : 2022.02.28

Abstract

Backgrounds/Aims: Mechanisms for the development of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients remain unclear. The aim of the present study was to identify genes and pathways involved in the development of HBV-associated HCC. Methods: The GSE121248 gene dataset, which included 70 HCCs and 37 adjacent liver tissues, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in HCCs and adjacent liver tissues were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were then performed. Results: Of 134 DEGs identified, 34 were up-regulated and 100 were down-regulated in HCCs. The 34 up-regulated DEGs were mainly involved in nuclear division, organelle fission, spindle and midbody formation, histone kinase activity, and p53 signaling pathway, whereas the 100 down-regulated DEGs were involved in steroid and hormone metabolism, collagen-coated extracellular matrix, oxidoreductase activity, and activity on paired donors, including incorporation or reduction of molecular oxygen, monooxygenase activity, and retinol metabolism. Analyses of protein-protein interaction networks with a high degree of connectivity identified significant modules containing 14 hub genes, including ANLN, ASPM, BUB1B, CCNB1, CDK1, CDKN3, ECT2, HMMR, NEK2, PBK, PRC1, RACGAP1, RRM2, and TOP2A, which were mainly associated with nuclear division, organelle fission, spindle formation, protein serine/threonine kinase activity, p53 signaling pathway, and cell cycle. Conclusions: This study identified key genes and carcinogenic pathways that play essential roles in the development of HBV-associated HCC. This may provide important information for the development of diagnostic and therapeutic targets for HCC.

Keywords

References

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