Single-nucleotide polymorphisms of stemness genes predicted to regulate RNA splicing, microRNA and oncogenic signaling are associated with prostate cancer survival

被引：9

作者：

Freedman, Jennifer A. ^{[1
,2
]}

Wang, Yanru ^{[1
,2
]}

Li, Xuechan ^{[2
]}

Liu, Hongliang ^{[1
,2
]}

Moorman, Patricia G. ^{[2
,3
]}

George, Daniel J. ^{[1
,2
]}

Lee, Norman H. ^{[4
]}

Hyslop, Terry ^{[2
,5
]}

Wei, Qingyi ^{[1
,2
]}

Patierno, Steven R. ^{[1
,2
]}

机构：

[1] Duke Univ, Med Ctr, Dept Med, Div Med Oncol, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC 27710 USA

[3] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA

[4] George Washington Univ, Sch Med & Hlth Sci, Dept Pharmacol & Physiol, Washington, DC 20037 USA

[5] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA

来源：

CARCINOGENESIS | 2018年 / 39卷 / 07期

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CELLS; RISK; IDENTIFICATION; METAANALYSIS; SELECTION; VARIANTS; ANTIGEN; MODEL;

D O I：

10.1093/carcin/bgy062

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Prostate cancer (PCa) is a clinically and molecularly heterogeneous disease, with variation in outcomes only partially predicted by grade and stage. Additional tools to distinguish indolent from aggressive disease are needed. Phenotypic characteristics of stemness correlate with poor cancer prognosis. Given this correlation, we identified single-nucleotide polymorphisms (SNPs) of stemness-related genes and examined their associations with PCa survival. SNPs within stemness-related genes were analyzed for association with overall survival of PCa in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Significant SNPs predicted to be functional were selected for linkage disequilibrium analysis and combined and stratified analyses. Identified SNPs were evaluated for association with gene expression. SNPs of CD44 (rs9666607), ABCC1 (rs35605 and rs212091) and GDF15 (rs1058587) were associated with PCa survival and predicted to be functional. A role for rs9666607 of CD44 and rs35605 of ABCC1 in RNA splicing regulation, rs212091 of ABCC1 in miRNA binding site activity and rs1058587 of GDF15 in causing an amino acid change was predicted. These SNPs represent potential novel prognostic markers for overall survival of PCa and support a contribution of the stemness pathway to PCa patient outcome.

引用

页码：879 / 888

页数：10

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