Single-nucleotide polymorphisms of stemness genes predicted to regulate RNA splicing, microRNA and oncogenic signaling are associated with prostate cancer survival
| Autor: | Steven R. Patierno, Xuechan Li, Daniel J. George, Hongliang Liu, Terry Hyslop, Qingyi Wei, Norman H. Lee, Patricia G. Moorman, Yanru Wang, Jennifer A. Freedman |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cancer Research Linkage disequilibrium Growth Differentiation Factor 15 Carcinogenesis RNA Splicing MiRNA binding Single-nucleotide polymorphism Biology medicine.disease_cause Polymorphism Single Nucleotide 03 medical and health sciences Prostate cancer 0302 clinical medicine microRNA Biomarkers Tumor medicine Humans Genetic Predisposition to Disease P-Chloroamphetamine Gene Cancer Biomarkers and Molecular Epidemiology Aged Aged 80 and over Prostate Prostatic Neoplasms Oncogenes General Medicine Middle Aged medicine.disease MicroRNAs Hyaluronan Receptors 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Multidrug Resistance-Associated Proteins Signal Transduction |
| Zdroj: | Carcinogenesis. 39:879-888 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgy062 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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