A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma
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 c...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1681 |
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| author | Chih-Lang Lin Kung-Hao Liang Ching-Chih Hu Cheng-Hung Chien Li-Wei Chen Rong-Nan Chien Yang-Hsiang Lin Chau-Ting Yeh |
| author_facet | Chih-Lang Lin Kung-Hao Liang Ching-Chih Hu Cheng-Hung Chien Li-Wei Chen Rong-Nan Chien Yang-Hsiang Lin Chau-Ting Yeh |
| author_sort | Chih-Lang Lin |
| collection | DOAJ |
| description | 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 (<i>p</i> = 2.2 × 10<sup>−7</sup>) 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 (<i>p</i> = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 “TT” genotype. |
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| language | English |
| last_indexed | 2024-03-09T12:18:08Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9be0c2aa91c94b4987b5bc3632c35bf42023-11-30T22:44:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242168110.3390/ijms24021681A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular CarcinomaChih-Lang Lin0Kung-Hao Liang1Ching-Chih Hu2Cheng-Hung Chien3Li-Wei Chen4Rong-Nan Chien5Yang-Hsiang Lin6Chau-Ting Yeh7Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, TaiwanDepartment of Medical Research, Taipei Veterans General Hospital, Taipei 112, TaiwanLiver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, TaiwanLiver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, TaiwanLiver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, TaiwanLiver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung 204, TaiwanLiver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanLiver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanSorafenib 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 (<i>p</i> = 2.2 × 10<sup>−7</sup>) 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 (<i>p</i> = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 “TT” genotype.https://www.mdpi.com/1422-0067/24/2/1681genome-wide association study (GWAS)advanced hepatocellular carcinoma (aHCC)overall survival (OS) |
| spellingShingle | Chih-Lang Lin Kung-Hao Liang Ching-Chih Hu Cheng-Hung Chien Li-Wei Chen Rong-Nan Chien Yang-Hsiang Lin Chau-Ting Yeh A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma International Journal of Molecular Sciences genome-wide association study (GWAS) advanced hepatocellular carcinoma (aHCC) overall survival (OS) |
| title | A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma |
| title_full | A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma |
| title_fullStr | A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma |
| title_full_unstemmed | A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma |
| title_short | A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma |
| title_sort | single nucleotide polymorphism rs1010816 predicts sorafenib therapeutic outcomes in advanced hepatocellular carcinoma |
| topic | genome-wide association study (GWAS) advanced hepatocellular carcinoma (aHCC) overall survival (OS) |
| url | https://www.mdpi.com/1422-0067/24/2/1681 |
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