{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:26:45Z","timestamp":1785432405758,"version":"3.56.0"},"reference-count":34,"publisher":"Baishideng Publishing Group Inc.","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Clin Oncol"],"abstract":"BACKGROUND<\/jats:p>\n Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, particularly in Egypt, where hepatitis C virus (HCV) prevalence is high. T cell exhaustion markers such as programmed death 1 (PD-1), T cell immunoglobulin and ITIM domain, and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) play a crucial role in HCC immune evasion; however, their expression patterns in Egyptian patients remain underexplored.<\/jats:p>\n AIM<\/jats:p>\n To characterize the expression of PD-1, T cell immunoglobulin and ITIM domain, and TIM-3 on CD4+ and CD8+ T cells across HCV-related liver disease stages and to determine their association with disease severity and survival in an Egyptian cohort.<\/jats:p>\n METHODS<\/jats:p>\n This prospective case-control study included 200 Egyptian participants: 50 with HCV-related HCC, 50 with HCV-related cirrhosis, 50 with chronic HCV infection, and 50 healthy controls (HCV-negative by polymerase chain reaction). Flow cytometry quantified immune exhaustion markers, and clinical data were analyzed using multivariate and survival modeling frameworks, adjusting for key confounders.<\/jats:p>\n RESULTS<\/jats:p>\n HCC patients showed significantly higher expression of all T-cell exhaustion markers than other groups (P < 0.001). Alpha-fetoprotein (AFP) levels were markedly elevated in HCC (median 13210 ng\/mL, P < 0.001). Marker expression showed strong positive correlations with Child-Pugh class, AFP, and Barcelona Clinic Liver Cancer stage, and a negative correlation with model for end-stage liver disease score (all P < 0.001). Non-survivors (34%) had higher marker expression and AFP levels than survivors (P < 0.001). Receiver operating characteristic analysis demonstrated excellent mortality prediction for CD4\/PD-1 [area under the curve (AUC) = 0.92] and AFP (AUC = 0.89), while combining AFP with CD8\/TIM-3 achieved the best accuracy (AUC = 0.95). Cox regression identified high CD8\/TIM-3 expression and Barcelona Clinic Liver Cancer stage D as independent mortality predictors, and CD4\/PD-1 partially mediated AFP\u2019s effect on mortality (\u03b2 = 0.45, P < 0.001).<\/jats:p>\n CONCLUSION<\/jats:p>\n Elevated T cell exhaustion markers were linked to advanced disease and poor survival in Egyptian patients with HCV-related HCC. Machine learning and mediation analyses identified CD4\/PD-1 and CD8\/TIM-3 as independent prognostic biomarkers, reinforcing their potential as therapeutic targets. These findings provide novel insights from a high-HCV-prevalence setting, supporting the integration of immune exhaustion profiling into risk stratification for HCC.<\/jats:p>","DOI":"10.5306\/wjco.v17.i2.114622","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T01:09:54Z","timestamp":1770340194000},"source":"Crossref","is-referenced-by-count":1,"title":["T cell exhaustion markers in hepatitis C virus-related hepatocellular carcinoma: Expression patterns and prognostic significance in an Egyptian cohort"],"prefix":"10.5306","volume":"17","author":[{"given":"Asmaa M","family":"Hasan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M F I","family":"Ghanem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira A A","family":"Othman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai Hamdy","family":"Rashad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahla","family":"Nosair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Elgamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.21608\/aeji.2021.98381.1183"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.21608\/ajbas.2025.362040.1251"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1912628"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v13.i12.1919"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nri1573"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2021.153485"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s43556-025-00267-6"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31046-2"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.01.010"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-019-02465-y"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/9781118715598.ch17"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i17.2461"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13186"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.061"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1186\/s43046-020-0016-x"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109599"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens13080681"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.20517\/2394-5079.2024.141"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-025-01308-4"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nri3862"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v7.i23.2449"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/15321819.2022.2137810"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1611365"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.06.017"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v15.i12.2138"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0316-z"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4161\/onci.1.1.18344"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajg.2012.06.004"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4103\/mmj.mmj_3_22"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.21608\/jmals.2023.329306"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30937-9"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00438-0"}],"container-title":["World 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