A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma
-
Published:2023-01-14
Issue:2
Volume:24
Page:1681
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Lin Chih-Lang, Liang Kung-HaoORCID, Hu Ching-Chih, Chien Cheng-Hung, Chen Li-WeiORCID, Chien Rong-Nan, Lin Yang-HsiangORCID, Yeh Chau-Ting
Abstract
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 × 10−7) was associated with sorafenib therapeutic response in aHCC patients. Kaplan–Meier analysis indicated that the “TT” 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 “TT” genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 “TT” genotype.
Funder
Medical Research Council, Chang Gung Memorial Hospital
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference39 articles.
1. 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. (2017). Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol., 3, 524–548. 2. A global view of hepatocellular carcinoma: Trends, risk, prevention and management;Yang;Nat. Rev. Gastroenterol. Hepatol.,2019 3. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide;Perz;J. Hepatol.,2006 4. Global patterns of hepatocellular carcinoma management from diagnosis to death: The BRIDGE Study;Park;Liver Int.,2015 5. The Defective Allele of Aldehyde Dehydrogenase 2 Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma;Huang;J. Cancer,2019
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|