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

Abstract

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.

Department

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Citation

Published Version (Please cite this version)

10.1093/carcin/bgy062

Publication Info

Freedman, Jennifer A, Yanru Wang, Xuechan Li, Hongliang Liu, Patricia G Moorman, Daniel J George, Norman H Lee, Terry Hyslop, et al. (2018). Single-nucleotide polymorphisms of stemness genes predicted to regulate RNA splicing, microRNA and oncogenic signaling are associated with prostate cancer survival. Carcinogenesis, 39(7). pp. 879–888. 10.1093/carcin/bgy062 Retrieved from https://hdl.handle.net/10161/18503.

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Scholars@Duke

Freedman

Jennifer Freedman

Associate Professor in Medicine
Moorman

Patricia Gripka Moorman

Professor Emeritus in Family Medicine and Community Health

Dr. Moorman's research focuses on the epidemiology of women's health issues. Her work includes research on ovarian cancer, breast cancer and hysterectomy. Areas of particular interest include disparities in cancer risk factors and outcomes and the effects of hysterectomy on ovarian function.  As part of the Duke Evidence Synthesis group, she has also been involved in systematic reviews and meta-analyses related to ovarian cancer, breast cancer and infertility.

Hyslop

Terry Hyslop

Adjunct Professor in the Department of Biostatistics & Bioinformatics
Wei

Qingyi Wei

Professor Emeritus in Population Health Sciences

Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and variations in cell death. He is Editor-in-Chief of the open access journal "Cancer Medicine" and Associate Editor-in-Chief of the International Journal of Molecular Epidemiology and Genetics.

Area of Expertise: Epidemiology

Patierno

Steven Patierno

Charles D. Watts Distinguished Professor of Medicine

Patierno's current translational research interests are focused on the genomics molecular biology of cancer disparities, cancer biology, molecular pharmacology and targeted experimental therapeutics to control prostate, breast and lung tumor aggressiveness. He is an internationally recognized expert in cancer control, cancer causation and molecular carcinogenesis, which includes a broad spectrum of laboratory and population level research.   Patierno is also actively engaged in cancer health disparities and healthcare delivery research focused on patient navigation, survivorship, community-based interventions, mHealth, implementation sciences, cancer care economics, and policy.


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