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Chronic infection induced by hepatitis B virus (HBV) is a prominent etiological factor influencing the development of HCC. Although recent advances in multi\u2010omics approaches have facilitated extensive exploration of HCC molecular characteristics, translating the characteristics of subtypes into clinical applications has been challenging due to parameters like limited sample size and complex classifiers for early detection. In the present study, we performed transcriptomics profiling of HBV\u2010infected HCC patient tissue data to gather comprehensive insights into the intricate molecular mechanisms underlying HBV\u2010associated HCC, specifically, viral protein interactions that influence the expression of oncogenes. The 1059 differentially expressed genes (DEGs) identified across two GEO data sets revealed upregulation of cell cycle and mitosis\u2010related genes, alongside downregulation of genes involved in fatty acid degradation and cytochrome P450 activity. CDK1 and CDC20 which are part of the top cluster and hub gene from interactome analysis were identified as potential markers for HBV\u2010positive HCC through gene expression pattern and overall survival analysis. Additionally, 19 DEGs showing significance in HCC development were identified as interacting partners with HBV proteins. Among them, the interaction of HBsAg with ALB and SHBG and their downregulation correlates to the lower testosterone levels identified in HBV and HCC patients. Together, the study enhances the understanding of the heterogeneity and molecular pathogenesis of HBV\u2010positive HCC.<\/jats:p>","DOI":"10.1111\/1348-0421.13219","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T12:38:01Z","timestamp":1744893481000},"page":"326-338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptome Profiling and Viral\u2212Human Interactome Insights Into HBV\u2010Driven Oncogenic Alterations in Hepatocellular Carcinoma"],"prefix":"10.1111","volume":"69","author":[{"given":"Anilkumar I.","family":"Ananthakrishnan","sequence":"first","affiliation":[{"name":"Center for Systems Biology and Molecular Medicine Yenepoya Research Centre, Yenepoya (Deemed to be University) Mangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Althaf","family":"Mahin","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics 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