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Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer.

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收录情况： ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越：领军期刊

作者：
Mao Chenxue[1,2] ; Chen Juan[1,2] ; Zou Ting[1,2] ; Zhou Yuankang[1,2] ; Liu Junyan[1,2] ; Li Xi[1,2] ; Li Xiangping[1] ; Li Min[3] ; Pan Pinhua[3] ; Zhuo Wei[1,2] ; Gao Yang[4] ; Hu Shuo[5] ; Xiao Desheng[6] ; Wu Lin[7] ; Wang Zhan[8] ; Xu Heng[9] ; Yang Wen[10] ; Xu Yingjie[10] ; Xiao Haihua[11] ; Hanada Kazuhiko[12] ; Zhang Wei[1,2] ; Zhou Honghao[1,2] ; Yin Jiye[1,2] ; Liu Zhaoqian[1,2] ;
机构： [1]Departments of Clinical Pharmacology and Pharmacy, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center forGeriatric Disorders, XiangyaHospital, Central SouthUniversity,Changsha 410008, China [2]Institute of Clinical Pharmacology, Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Central South University, Changsha 410078, China [3]Department of Respiratory, Xiangya Hospital, Central South University, Changsha 410008, China [4]Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, China [5]Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha 410008, China [6]Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China [7]Department of Thoracic Medicine, Hunan Cancer Hospital, Changsha 410014, China [8]Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Changsha 410014, China [9]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610000, China [10]Department of Molecular and Cellular Biochemistry, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China [11]Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China [12]Department of Pharmacometrics and Pharmacokinetics Meiji Pharmaceutical University, Tokyo 204-8588, Japan
出处：
DOI： 10.1016/j.apsb.2021.10.007
ISSN：

摘要：
To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

基金：
This work was supported by the National Key Research and Development Programs (2016YFC1306900 and 2017ZX09304- 014, China), National Natural Science Foundation of China (81573508, 81874327, 81773823, 81803640 and 82073943, China), Fundamental Research Funds for the Central Universities of Central South University (2018zzts251, China), The Strategy- Oriented Special Project of Central South University in China (ZLXD2017003), Youth Science Foundation of Xiangya Hospital, Central South University (2017Q02, China) and Hunan Cancer Hospital Climb Plan (YF2020011, China).
语种：
外文
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出版当年[2022]版：
大类 | 1 区 化学
小类 | 1 区 药学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 药学
第一作者：
第一作者机构： [1]Departments of Clinical Pharmacology and Pharmacy, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center forGeriatric Disorders, XiangyaHospital, Central SouthUniversity,Changsha 410008, China [2]Institute of Clinical Pharmacology, Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Central South University, Changsha 410078, China
共同第一作者：
通讯作者：
通讯机构： [1]Departments of Clinical Pharmacology and Pharmacy, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center forGeriatric Disorders, XiangyaHospital, Central SouthUniversity,Changsha 410008, China [2]Institute of Clinical Pharmacology, Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Central South University, Changsha 410078, China
推荐引用方式(GB/T 7714)：
Mao Chenxue,Chen Juan,Zou Ting,et al.Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer.[J].Acta Pharmaceutica Sinica B.2022,12(3):1514-1522.doi:10.1016/j.apsb.2021.10.007.
APA：
Mao Chenxue,Chen Juan,Zou Ting,Zhou Yuankang,Liu Junyan...&Liu Zhaoqian.(2022).Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer..Acta Pharmaceutica Sinica B,12,(3)
MLA：
Mao Chenxue,et al."Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer.".Acta Pharmaceutica Sinica B 12..3(2022):1514-1522

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