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

TitleGermline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome‐Wide Association Study in Multiple Cohorts
Authors
Keywordsbiomarkers
cancer prognosis
germline polymorphisms
nasopharyngeal carcinoma
RPA1
Issue Date2020
PublisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844
Citation
Advanced Science, 2020, v. 7 n. 10, p. article no. 1903727 How to Cite?
AbstractGermline 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.
Persistent Identifierhttp://hdl.handle.net/10722/286197
ISSN
2018 Impact Factor: 15.804

 

DC FieldValueLanguage
dc.contributor.authorGuo, YM-
dc.contributor.authorChen, JR-
dc.contributor.authorFeng, YC-
dc.contributor.authorChua, MLK-
dc.contributor.authorZeng, Y-
dc.contributor.authorHui, EP-
dc.contributor.authorChan, AKC-
dc.contributor.authorTang, LQ-
dc.contributor.authorWang, L-
dc.contributor.authorCui, Q-
dc.contributor.authorHan, HQ-
dc.contributor.authorLuo, CL-
dc.contributor.authorLin, GW-
dc.contributor.authorLiang, Y-
dc.contributor.authorLiu, Y-
dc.contributor.authorHe, ZL-
dc.contributor.authorLiu, YX-
dc.contributor.authorWei, PP-
dc.contributor.authorLiu, CJ-
dc.contributor.authorPeng, W-
dc.contributor.authorHan, BW-
dc.contributor.authorZuo, XY-
dc.contributor.authorOng, EHW-
dc.contributor.authorYeo, ELL-
dc.contributor.authorLow, KP-
dc.contributor.authorTan, GS-
dc.contributor.authorLim, TKH-
dc.contributor.authorHwang, JSG-
dc.contributor.authorLi, B-
dc.contributor.authorFeng, QS-
dc.contributor.authorXia, X-
dc.contributor.authorXia, YF-
dc.contributor.authorKo, J-
dc.contributor.authorDai, W-
dc.contributor.authorLung, ML-
dc.contributor.authorChan, ATC-
dc.contributor.authorLo, DYM-
dc.contributor.authorZeng, MS-
dc.contributor.authorMai, HQ-
dc.contributor.authorLiu, J-
dc.contributor.authorZeng, YX-
dc.contributor.authorBei, JX-
dc.date.accessioned2020-08-31T07:00:31Z-
dc.date.available2020-08-31T07:00:31Z-
dc.date.issued2020-
dc.identifier.citationAdvanced Science, 2020, v. 7 n. 10, p. article no. 1903727-
dc.identifier.issn2198-3844-
dc.identifier.urihttp://hdl.handle.net/10722/286197-
dc.description.abstractGermline 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.-
dc.languageeng-
dc.publisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844-
dc.relation.ispartofAdvanced Science-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectbiomarkers-
dc.subjectcancer prognosis-
dc.subjectgermline polymorphisms-
dc.subjectnasopharyngeal carcinoma-
dc.subjectRPA1-
dc.titleGermline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome‐Wide Association Study in Multiple Cohorts-
dc.typeArticle-
dc.identifier.emailKo, J: joko@hku.hk-
dc.identifier.emailDai, W: weidai2@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityKo, J=rp02011-
dc.identifier.authorityDai, W=rp02146-
dc.identifier.authorityLung, ML=rp00300-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/advs.201903727-
dc.identifier.scopuseid_2-s2.0-85082081732-
dc.identifier.hkuros313299-
dc.identifier.volume7-
dc.identifier.issue10-
dc.identifier.spagearticle no. 1903727-
dc.identifier.epagearticle no. 1903727-
dc.publisher.placeGermany-

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