{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:46:16Z","timestamp":1760147176445,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T00:00:00Z","timestamp":1673654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council, Chang Gung Memorial Hospital","award":["CMRPG2J0011","CMRPG2K0083","CLRPG2L0052","CRRPG2H0045","NRRPG2L0011"],"award-info":[{"award-number":["CMRPG2J0011","CMRPG2K0083","CLRPG2L0052","CRRPG2H0045","NRRPG2L0011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sorafenib is currently a targeted agent widely used in the treatment of advanced hepatocellular carcinoma (aHCC). However, to date there is still a lack of a reliable marker capable of predicting sorafenib therapeutic responses. Here, we conducted a genome-wide association study (GWAS) to identify candidate single-nucleotide polymorphism outcome predictors in aHCC patients. A total of 74 real-world sorafenib-treated aHCC patients were enrolled for GWAS and outcome analysis. GWAS showed that rs1010816 (p = 2.2 \u00d7 10\u22127) was associated with sorafenib therapeutic response in aHCC patients. Kaplan\u2013Meier analysis indicated that the \u201cTT\u201d genotype was significantly associated with a favorable therapeutic response but not significantly associated with overall survival (OS). Univariate followed by multivariate Cox proportional hazard analysis showed that ascites, main portal vein thrombosis, lower platelet count, lower total sorafenib doses, higher PALBI score in model A and higher ALBI grade in model B were significantly associated with a shorter OS. Subgroup analysis showed that only in alcoholic aHCC patients treated by sorafenib, rs1010816 \u201cTT\u201d genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 \u201cTT\u201d genotype.<\/jats:p>","DOI":"10.3390\/ijms24021681","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:29:55Z","timestamp":1673836195000},"page":"1681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"24","author":[{"given":"Chih-Lang","family":"Lin","sequence":"first","affiliation":[{"name":"Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan"},{"name":"Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"},{"name":"Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7593-5965","authenticated-orcid":false,"given":"Kung-Hao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan"},{"name":"Institute of Food Safety and Health Risk Assessment, National Yang-Ming Chiao-Tung University, Taipei 112, Taiwan"},{"name":"Institute of Biomedical Informatics, National Yang-Ming Chiao-Tung University, Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Chih","family":"Hu","sequence":"additional","affiliation":[{"name":"Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9596-9209","authenticated-orcid":false,"given":"Cheng-Hung","family":"Chien","sequence":"additional","affiliation":[{"name":"Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8805-2275","authenticated-orcid":false,"given":"Li-Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong-Nan","family":"Chien","sequence":"additional","affiliation":[{"name":"Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan"},{"name":"Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"},{"name":"Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4295-6062","authenticated-orcid":false,"given":"Yang-Hsiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chau-Ting","family":"Yeh","sequence":"additional","affiliation":[{"name":"Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,14]]},"reference":[{"key":"ref_1","unstructured":"Global Burden of Disease Cancer Collaboration, Fitzmaurice, C., Allen, C., Barber, R.M., Barregard, L., Bhutta, Z.A., Brenner, H., Dicker, D.J., Chimed-Orchir, O., and Dandona, R. 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