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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is one of the malignant tumors with high incidence and mortality rates worldwide. Given the poor prognosis of patients with HCC, it is crucial to explore the molecular mechanisms underlying HCC development and to evaluate prognostic markers. Differential expression analysis followed by univariate Cox, LASSO, and multivariate Cox regression identified four genes (EPO, SOCS2, IL18RAP, and KPNA2), and a Cox-based risk score was evaluated in the TCGA-LIHC cohort and externally in GSE14520 using Kaplan\u2013Meier and time-dependent ROC analyses. Bulk, single-cell, and protein resources provided convergent expression context. Survival machine-learning analysis using observed overall-survival time and censoring status identified Cox\u2013Ridge as the best-performing model in TCGA-LIHC, with more modest performance in GSE14520, and immune profiling revealed risk-group-associated differences in estimated immune and stromal components, immune-cell composition, and immune-checkpoint expression. The oncoPredict\/GDSC2 screen highlighted five potential drug candidates for experimental prioritization. Because the drug screen is based on computationally predicted sensitivities, these findings should be regarded as hypothesis-generating and require validation in prospective cohorts and experimental systems before clinical translation.<\/jats:p>","DOI":"10.3390\/ijms27177535","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"7535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Transcriptomic Analyses Identify Four Prognosis-Associated Genes in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1458-9648","authenticated-orcid":false,"given":"Yuxian","family":"Liu","sequence":"first","affiliation":[{"name":"School of Artificial Intelligence, Anhui University of Science & Technology, Huainan 232001, China"},{"name":"State Key Laboratory of Digital Intelligent Technology for Unmanned Coal Mining, Anhui University of Science & Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingjie","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Anhui University of Science & Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Anhui University of Science & Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Anhui University of Science & Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Anhui University of Science & Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangcheng","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Anhui University of Science & Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6265-2862","authenticated-orcid":false,"given":"Hao","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory for Neuro-Information of Ministry of Education, Center for Informational Biology, School of Life Sciences and Technology, University of Electronic Science and Technology of China, Chengdu 611731, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1508-4131","authenticated-orcid":false,"given":"Yanni","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Anhui University of Science & Technology, Huainan 232001, China"},{"name":"State Key Laboratory of Digital Intelligent Technology for Unmanned Coal Mining, Anhui University of Science & Technology, Huainan 232001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s10555-023-10084-4","article-title":"Hepatocellular carcinoma: Molecular mechanism, targeted therapy, and biomarkers","volume":"42","author":"Wang","year":"2023","journal-title":"Cancer Metastasis Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.scib.2025.12.022","article-title":"Global, regional, and national burden of hepatocellular carcinoma and contribution of nine modifiable risk factors across 185 countries\/territories in 2022","volume":"71","author":"Li","year":"2026","journal-title":"Sci. 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