Network-based analysis of candidate oncogenes and pathways in hepatocellular carcinoma
Makaleler > Tam Makale · 2025
Yazarlar: Nasim Rahimi-Farsi, Taha Shahbazi, Abozar Ghorbani, Negar Mottaghi-Dastjerdi, Fateme Yazdani, Parvin Mohseni, Pietro Hiram Guzzi, Gita Esmail nia, Behzad Shahbazi, Khadijeh Ahmadi
Biochemistry and Biophysics Reports, Uluslararası, Scopus, 2025, cilt 43, ss 102086-102086
DOI: 10.1016/j.bbrep.2025.102086
Özet
Hepatocellular carcinoma (HCC) is a major worldwide health burden due to poor outcomes. Identifying dysregulated molecular circuits in HCC is critical for developing precise treatments. A systems-level approach using multi-omics data is required to reveal the intricate non-linear interactions underlying liver carcinogenesis. Both tumor and control tissues contained differentially expressed genes (DEGs). Hub genes with the strongest connection were identified as potential drivers. Protein-protein interaction (PPI) mapping verified hub connectivity. Perturbed functions were evaluated using Gene Ontology and KEGG pathway enrichment analysis. Cytoscape clustering separated the interactome into modules. Motif discovery indicated a shift in cis -regulatory logic. Expression analysis, survival analysis, and drug screening were performed on the hub genes. Network hub gene analysis identified 11 hub genes, including DLGAP5, KIF23, KIF11, CCNB1, CDK1, BRCA1, CCNA2, SHCBP1, KIAA0101, FAM83D, and SPC25. Gene set enrichment analysis (GSEA) revealed dysregulation in cell cycle progression, DNA damage response, and metabolic pathways, and an association of these genes with reduced overall survival in HCC patients. Also, drug screening identified potential therapeutic agents targeting these hub genes.The findings increase mechanistic understanding with potential clinical applications. Future validation studies that include multi-omic data may strengthen current hypotheses and enable targeted therapy design against crucial in HCC. • Reconstructed a PPI network for the DEGs and applied centrality measures to pinpoint key hub genes. • Performed promoter analysis on the hub genes to uncover functional roles in gene regulation. • Conducted molecular docking studies to evaluate the binding interactions between approved drugs and the hub proteins KIF11 and CDK1. • Analyzed age and gender related differences in the expression of the identified hub genes.