Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome-Wide Association Study in Multiple Cohorts

Submit Time: 2020-03-06

Author: Yun-Miao Guo 1 ; Jie-Rong Chen 1,2 ; Yan-Chun Feng 1 ; Chua, Melvin L. K. 3,4 ; Zeng, Yanni 1,5,6,7 ; Edwin Pun Hui 8 ; Allen K. C. Chan 9 ; Lin-Quan Tang 1 ; Lin Wang 1 ; Qian Cui 2 ; Hui-Qiong Han 10 ; Chun-Ling Luo 1 ; Guo-Wang Lin 1 ; Yan Liang 1 ; Yang Liu 1 ; Zhong-Lian He 1 ; Yu-Xiang Liu 1 ; Pan-Pan Wei 1 ; Chu-Jun Liu 1 ; Wan Peng 1 ; Bo-Wei Han 1 ; Xiao-Yu Zuo 1 ; Enya H. W. Ong 3,4 ; Eugenia L. L. Yeo 3,4 ; Kar Perng Low 3,4 ; Gek San Tan 11 ; Tony K. H. Lim 12 ; Jacqueline S. G. Hwang 12 ; Bo Li 13,14 ; Qi-Sheng Feng 1 ; Xiaojun Xia 1 ; Yun-Fei Xia 1 ; Josephine Ko 15 ; Wei Dai 15 ; Maria Li Lung 15 ; Anthony T. C. Chan 8 ; Dennis Y. M. Lo 9 ; Mu-Sheng Zeng 1 ; Hai-Qiang Mai 1 ; Jianjun Liu 2,16 ; Yi-Xin Zeng 1 ; Jin-Xin Bei 1,17 ;

Institute: 1.Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, P. R. China; 2.Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P. R. China; 3.Division of Radiation Oncology and Division of Medical Sciences, National Cancer Centre Singapore, Singapore 169610; 4.Duke-NUS Medical School, Singapore 169857; 5.Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, P. R. China; 6.Guangdong Province Translational Forensic Medicine Engineering Technology Research Centre，Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, P. R. China; 7.Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, P. R. China; 8.Department of Clinical Oncology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR; 9.Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong SAR; 10.Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China; 11.Translational Pathology Centre, Department of Molecular Pathology, Singapore General Hospital, Singapore 169856; 12.Department of Anatomical Pathology, Singapore General Hospital, Singapore 169856; 13.Department of Biochemistry and Molecular Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, P. R. China; 14.RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, P. R. China; 15.Department of Clinical Oncology, University of Hong Kong, Hong Kong SAR; 16.Genome Institute of Singapore, Genome Building, Singapore 138672; 17.Centre for Precision Medicine, Sun Yat-sen University, Guangzhou 510080, P. R. China;

Abstracts

Germline polymorphisms have been linked with differential survival outcomes in cancers but have not been well studied in nasopharyngeal carcinoma (NPC). Here, two-phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome-wide genotypes at 246,173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazards regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta-analysis of all samples (n = 5,553) confirm that the presence of rs1131636-T, located in the 3′-UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20-1.47, P = 6.31 × 10-8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promoted the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR-1253 has been identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.

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From: 贝锦新

Subject: Medicine, Pharmacy >> Clinical Medicine

DOI：10.1002/advs.201903727

Keywords: Nasopharyngeal carcinoma; Prognosis; Overall survival; Single nucleotide polymorphism; RPA1;

Journal:Advanced Science

Cite as: chinaXiv:202003.00008 (or this versionchinaXiv:202003.00008V3)

Recommended references： Yun-Miao Guo,Jie-Rong Chen,Yan-Chun Feng,Chua, Melvin L. K. ,Zeng, Yanni ,Edwin Pun Hui,Allen K. C. Chan,Lin-Quan Tang,Lin Wang,Qian Cui,Hui-Qiong Han,Chun-Ling Luo,Guo-Wang Lin,Yan Liang,Yang Liu,Zhong-Lian He,Yu-Xiang Liu,Pan-Pan Wei,Chu-Jun Liu,Wan Peng,Bo-Wei Han,Xiao-Yu Zuo,Enya H. W. Ong,Eugenia L. L. Yeo,Kar Perng Low,Gek San Tan ,Tony K. H. Lim,Jacqueline S. G. Hwang,Bo Li,Qi-Sheng Feng,Xiaojun Xia,Yun-Fei Xia,Josephine Ko,Wei Dai,Maria Li Lung,Anthony T. C. Chan,Dennis Y. M. Lo,Mu-Sheng Zeng,Hai-Qiang Mai,Jianjun Liu,Yi-Xin Zeng,Jin-Xin Bei.(2020).Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome-Wide Association Study in Multiple Cohorts.Advanced Science.doi:10.1002/advs.201903727 (Click&Copy)

Version History
[V3]	2020-03-06 18:52:44	chinaXiv:202003.00008V3	Download
[V2]	2020-03-06 11:46:14	chinaXiv:202003.00008v2(View This Version)	Download
[V1]	2020-02-28 23:35:37	chinaXiv:202003.00008v1(View This Version)	Download

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