| Autor: |
Yun‐Miao Guo, Jie‐Rong Chen, Yan‐Chun Feng, Melvin L. K. Chua, Yanni Zeng, 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 L. Lung, Anthony T. C. Chan, Dennis Y. M. Lo, Mu‐Sheng Zeng, Hai‐Qiang Mai, Jianjun Liu, Yi‐Xin Zeng, Jin‐Xin Bei |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Advanced Science, Vol 7, Iss 10, Pp n/a-n/a (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.201903727 |
| Popis: |
Abstract Germline polymorphisms are linked with differential survival outcomes in cancers but are not well studied in nasopharyngeal carcinoma (NPC). Here, a 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 hazard regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta‐analysis of all samples (n = 5553) confirms 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 promotes the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR‐1253 is 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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