• Identification of hub Genes and pathways in hepatitis B virus-associated hepatocellular carcinoma
  • Niloufar sadat Kalaki,1,* Nazila Ghasemi,2 Mozhgan Ahmadzadeh,3
    1. Department of cellular and molecular biology, faculty of biological sciences, kharazmi university, Tehran, Iran
    2. Department of biology, Jahrom branch, Islamic Azad University, Jahrom, Iran
    3. Department of cellular and molecular biology, faculty of biological sciences, kharazmi university, Tehran, Iran


  • Introduction: The hepatitis B virus is one of the most common causes of liver cancer in the world. This study will assist us in providing effective treatment by gaining a better understanding of the mechanisms involved in the development and progression of HBV-related cancer. By identifying hub genes and the pathways related to their functions, we can improve the diagnostics and treatment of diseases.
  • Methods: An analysis of GSE83148 from the Gene Expression Omnibus (GEO) site was carried out as part of this study. In this study, we were able to identify DEGs with a p-value < 0.02 and a log ∣FC∣ >1.9 by normalizing the data using R software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases were used to identify pathways involved in the process of hepatocellular carcinoma development. We performed an analysis of protein-protein interactions (PPIs) by using the software Cytoscap and Gephi to identify the hub genes based on the results of the PPI analyses. A GEPIA analysis was carried out to be able to confirm the biomarkers and the target genes used in this study. 
  • Results: A total of 418 DEGs have been identified. Through the use of PPI, 96 hub genes were identified. According to the results of the GEPIA analysis, 3 genes with higher levels of expression in tumor samples have been identified as biomarkers, such as PPP2R1A (p < 0.05), TPR (p < 0.05) and TYMS (p < 0.05). It has been found that these biomarkers are involved in pathways related to Positive Regulation Of Protein Import Into Nucleus, Protein-Containing Complex Organization, one carbon metabolism and AMPK . There was a possibility of increasing survival rates by targeting genes like MTHFR (p = 0.0026) and RHEB (p = 0.016). by targeting these genes and reducing their expression, it was possible to increase survival rates, There are a number of pathways involved in target genes, including Autophagosome Membrane Docking ,Methionine Metabolic Process, Cellular senescence, and Endocytosis.
  • Conclusion: We concluded that the integrated bioinformatics approach was effective in revealing the pathways involved in the development process of HCC. By identifying hub genes. It will be possible to detect this disease at the earliest stages of the disease, and with the identification of target genes, it has been possible to increase survival rates.
  • Keywords: Hepatocellular carcinoma, HBV, PPI network, Diagnostic biomarkers, Cancer targeted therapy