A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma

被引:2
作者
Lin, Chih-Lang [1 ,2 ,3 ,4 ]
Liang, Kung-Hao [5 ,6 ,7 ]
Hu, Ching-Chih [1 ,4 ]
Chien, Cheng-Hung [1 ,4 ]
Chen, Li-Wei [1 ,4 ]
Chien, Rong-Nan [1 ,2 ,3 ,4 ]
Lin, Yang-Hsiang [2 ]
Yeh, Chau-Ting [2 ,4 ]
机构
[1] Keelung Chang Gung Mem Hosp, Liver Res Unit, Keelung 204, Taiwan
[2] Chang Gung Mem Hosp, Liver Res Ctr, Taoyuan 333, Taiwan
[3] Keelung Chang Gung Mem Hosp, Community Med Res Ctr, Keelung 204, Taiwan
[4] Chang Gung Univ, Coll Med, Taoyuan 333, Taiwan
[5] Taipei Vet Gen Hosp, Dept Med Res, Taipei 112, Taiwan
[6] Natl Yang Ming Chiao Tung Univ, Inst Food Safety & Hlth Risk Assessment, Taipei 112, Taiwan
[7] Natl Yang Ming Chiao Tung Univ, Inst Biomed Informat, Taipei 112, Taiwan
基金
英国医学研究理事会;
关键词
genome-wide association study (GWAS); advanced hepatocellular carcinoma (aHCC); overall survival (OS); ATEZOLIZUMAB PLUS BEVACIZUMAB; SIMPLE NONINVASIVE INDEX; ALPHA-FETOPROTEIN; SIGNIFICANT FIBROSIS; CLINICAL-PRACTICE; GALNT14; GENOTYPE; CHILD-PUGH; CHEMOTHERAPY; MANAGEMENT; MORTALITY;
D O I
10.3390/ijms24021681
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 x 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.
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页数:14
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