620 INTEGRATIVE GENOMIC ANALYSIS OF PROSTATE CANCER DISPARITIES BETWEEN AFRICAN AMERICAN AND CAUCASIAN AMERICAN POPULATIONS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011620 INTEGRATIVE GENOMIC ANALYSIS OF PROSTATE CANCER DISPARITIES BETWEEN AFRICAN AMERICAN AND CAUCASIAN AMERICAN POPULATIONS Bi-Dar Wang, Ramez Andrawis, Faisal Ahmed, Fernando Bianco, Thomas Jarrett, Harold Frazier, Steven Patierno, and Norman Lee Bi-Dar WangBi-Dar Wang Washington, DC More articles by this author , Ramez AndrawisRamez Andrawis Washington, DC More articles by this author , Faisal AhmedFaisal Ahmed Washington, DC More articles by this author , Fernando BiancoFernando Bianco Miami Beach, FL More articles by this author , Thomas JarrettThomas Jarrett Washington, DC More articles by this author , Harold FrazierHarold Frazier Washington, DC More articles by this author , Steven PatiernoSteven Patierno Washington, DC More articles by this author , and Norman LeeNorman Lee Washington, DC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1473AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) is a disease conferred by gene mutations, numerous alternations in gene expression and aberrant changes in genome composition/architecture. An area of research that continues to garner attention is PCa health disparities, wherein the African American (AA) population exhibits higher incidence and mortality rates compared to Caucasian Americans (CA). METHODS To identify the genetic predispositions and oncogenic networks associated with the observed PCa disparities, we applied a systems biology approach by integrating exon, microRNA and SNP information from PCa specimens of AA and CA patients. RNA and DNA purified from PCa (with Gleason score > 6) and patient-matched normal prostate needle biopsies from AAs and CAs were processed and hybridized onto Affymetrix human Exon 1.0 ST, SNP 6.0 arrays or Agilent human microRNA arrays. A 4-way statistical design (10% FDR, >1.5 fold-change) was employed to identify differentially expressed mRNAs in the following comparisons: AA normal vs. CA normal, AA cancer vs. CA cancer, AA cancer vs. AA normal, and CA cancer vs. CA normal. RESULTS Pathway analyses of the differentially expressed genes have revealed several critical network-level rewiring of gene interactions accounting for PCa disparities between AA and CA. The mis-regulated testosterone metabolism network in normal AA prostate tissues may represent a genetic predisposition factor in the AA. The inflammatory response (NF-KappaB network), activated oncogenic signaling pathways (ERK, JNK and p38), and up-regulated cancer promoting genes (RHOA and STAT1) may be associated with the higher recurrence and death rates in AA. Moreover, our exon and SNP profiling results have identified hundreds of genes exhibiting differential splicing patterns and/or copy number variations (CNVs) in AA and CA patients. Notably, at least 13 genes residing within the 5 oncogenic signaling pathways have been identified as exhibiting either differential mRNA splicing or CNVs between AA and CA PCa specimens. In addition, microRNA profiling further revealed that 14 microRNAs were differentially expressed in AA and CA cancer samples, potentially related to cell proliferation, anti-apoptosis, cell cycle regulation in AA cancers. CONCLUSIONS Our data suggest that mRNA splicing, CNVs, deregulated microRNA expression and gene-network rewiring may be critical in PCa health disparities between the AA and CA. These findings may facilitate the development of novel strategies for PCa detection, diagnosis, prognosis, and therapy in AA population. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e249-e250 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bi-Dar Wang Washington, DC More articles by this author Ramez Andrawis Washington, DC More articles by this author Faisal Ahmed Washington, DC More articles by this author Fernando Bianco Miami Beach, FL More articles by this author Thomas Jarrett Washington, DC More articles by this author Harold Frazier Washington, DC More articles by this author Steven Patierno Washington, DC More articles by this author Norman Lee Washington, DC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...