You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011141 GENE EXPRESSION PATHWAYS OF HIGH GRADE LOCALIZED PROSTATE CANCER Ashley E. Ross, Luigi Marchionni, Milena Vuica-Ross, Chris Cheadle, Jinshui Fan, David M. Berman, and Edward M. Schaeffer Ashley E. RossAshley E. Ross Baltimore, MD More articles by this author , Luigi MarchionniLuigi Marchionni Baltimore, MD More articles by this author , Milena Vuica-RossMilena Vuica-Ross Baltimore, MD More articles by this author , Chris CheadleChris Cheadle Baltimore, MD More articles by this author , Jinshui FanJinshui Fan Baltimore, MD More articles by this author , David M. BermanDavid M. Berman Baltimore, MD More articles by this author , and Edward M. SchaefferEdward M. Schaeffer Baltimore, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.208AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Despite advances in screening and local therapy, prostate cancer remains the second most common cause of cancer related death among American men, with those having Gleason sum 8–10 disease being at highest risk. Here we determine the gene expression pathways of high grade pathologically localized prostate cancer. METHODS Cancer cells from Gleason 3+3=6 or 4+4=8 tumors of men with localized disease were isolated by laser capture micro-dissection. Expression profiling was conducted across 18,344 unique annotated genes and data were analyzed using packages from the R/Bioconductor project to determine differential gene expression and perform gene set enrichment analysis. Publically available expression data was retrieved and analyzed individually in the same manner and in cross platform meta-analyses. RESULTS 670 genes were differentially expressed between Gleason sum 6 and 8 tumors with a false discovery rate of <5% (p<0.0014) including multiple genes previously shown to mediate prostate cancer survival, proliferation and metastasis in in vitro and xenograft models. Functional grouping of the differentially expressed genes revealed roles for developmental processes, signal transduction and embryonic stem cell pathways. Enrichment was seen for canonical members of the androgen receptor, EGFR, TNF-alpha and NOTCH signaling cascades. CONCLUSIONS In addition to androgen receptor signaling, growth factor and cytokine mediated pathways are activated in clinically localized high grade prostate cancer. The availability of therapeutics that selectively target these pathways encourages the development of clinical trials for their selective use in the neoadjuvant or adjuvant setting in men at high risk for disease progression. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e59-e60 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ashley E. Ross Baltimore, MD More articles by this author Luigi Marchionni Baltimore, MD More articles by this author Milena Vuica-Ross Baltimore, MD More articles by this author Chris Cheadle Baltimore, MD More articles by this author Jinshui Fan Baltimore, MD More articles by this author David M. Berman Baltimore, MD More articles by this author Edward M. Schaeffer Baltimore, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...