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Despite the high efficacy of direct-acting antivirals (DAAs) in eradicating HCV, HCC may still develop after sustained virological response (SVR), suggesting that HCV may leave behind lasting epigenetic and immunological alterations that sustain oncogenic risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to investigate the expression profiles of SOX9, TNFAIP3, and FOSL2 in peripheral blood mononuclear cells (PBMCs) and liver tissues from HCV-related HCC patients and to explore, through in silico analyses, their molecular and immunological roles in HCV-driven hepatocarcinogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Gene expression was quantified in PBMCs and liver tissues using RT-qPCR. Receiver operating characteristic (ROC) curve analyses assessed diagnostic potential. In silico analyses evaluated protein-protein interactions, gene-gene networks, epigenetic modifications, and correlations with immune cell infiltration and immunomodulatory molecules using publicly available datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SOX9, TNFAIP3, and FOSL2 were identified as interconnected regulators within NF-\u03baB and TGF-\u03b2 pathways, enriched in inflammatory and infection-related processes, and epigenetically modulated via promoter hypermethylation and histone remodeling. Their expression strongly correlated with macrophages, T cells, dendritic cells, and key immune modulators. RT-qPCR validation confirmed overexpression of SOX9 and TNFAIP3 in PBMCs and liver tissues from HCV-HCC patients, with PBMC levels closely reflecting tissue expression, and ROC analyses highlighted their potential as non-invasive biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SOX9 and TNFAIP3 emerge as key mediators linking persistent epigenetic alterations with immune remodeling in HCV-related HCC, and as potential non-invasive biomarkers for evaluation of HCC risk and post-DAA surveillance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13027-026-00735-w","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T10:24:29Z","timestamp":1771496669000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SOX9 and TNFAIP3 dysregulation in HCV-associated HCC after DAA therapy: insights into post-viral oncogenic memory"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8277-8304","authenticated-orcid":false,"given":"Rehab I.","family":"Moustafa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Farouk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Elsayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hend I.","family":"Shousha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha M.","family":"Elbrashy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Gabr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Yousif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Ramadan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Yosry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf O.","family":"Abdelaziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Abdelaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha G.","family":"Bader El Din","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"735_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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