1313 MICRORNA EXPRESSION PROFILING OF DIFFERENT GLEASON GRADES IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 20121313 MICRORNA EXPRESSION PROFILING OF DIFFERENT GLEASON GRADES IN PROSTATE CANCER Naveen Kachroo, Ajay Joseph, Lorenz Wernisch, Anne Warren, Tania Valencia, and Vincent Gnanapragasam Naveen KachrooNaveen Kachroo Cambridge, United Kingdom More articles by this author , Ajay JosephAjay Joseph Cambridge, United Kingdom More articles by this author , Lorenz WernischLorenz Wernisch Cambridge, United Kingdom More articles by this author , Anne WarrenAnne Warren Cambridge, United Kingdom More articles by this author , Tania ValenciaTania Valencia Cambridge, United Kingdom More articles by this author , and Vincent GnanapragasamVincent Gnanapragasam Cambridge, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1660AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The Gleason grade is a crucial pathological assessment of the aggressiveness of prostate cancer. The specific mechanisms that result in the evolution of higher Gleason grades however are currently unknown. MicroRNAs are small non-coding RNAs that regulate key cellular biological processes including tumour development. This study investigated if there were distinct microRNAs expressed in prostate tumours of different Gleason grades. METHODS Enriched benign and tumour populations of Gleason grade 3, 4 and 5 foci (pre-marked by a uropathologist) were isolated by laser capture microdissection from formalin fixed paraffin embedded diagnostic prostate needle biopsies of 36 men using a previously published method. MicroRNA expression profiling of the benign (n=9), Gleason 3 (n=9), Gleason 4 (n=9) and Gleason 5 (n=9) samples was performed using the Illumina human miRNA expression array. Bioinformatic analysis was performed with R statistical software, employing strict ranking criteria to profile microRNAs stratified by different tumour grades. RESULTS Hierarchical cluster analysis identified clustering of microRNA expression of benign glands with Gleason 3 tumours and Gleason 4 with Gleason 5 tumours. 39 microRNAs were differentially expressed in the Gleason 4/5 tumours compared to the Gleason 3/benign samples at a p<0.005 significance level. Functional gene target analysis using web based computational algorithms (Targetscan and microrna.org) was then performed for the top 9 altered microRNAs. Upregulated microRNA targets included genes involved in suppressing cell cycle regulation as well as migration and invasion. Conversely, down regulated microRNAs had putative target genes involved in promoting epithelial to mesenchymal transition and invasion. CONCLUSIONS This is the first study to investigate microRNA expression in specific Gleason grades. Our analysis has shown similarities in microRNAs expressed in benign and Gleason 3 foci as opposed to Gleason 4 and 5 foci. A dysregulated 9 microRNA expression panel, discriminatory for high Gleason grades, highlight potential mechanisms driving the development of aggressive high grade prostate tumours. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e532 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naveen Kachroo Cambridge, United Kingdom More articles by this author Ajay Joseph Cambridge, United Kingdom More articles by this author Lorenz Wernisch Cambridge, United Kingdom More articles by this author Anne Warren Cambridge, United Kingdom More articles by this author Tania Valencia Cambridge, United Kingdom More articles by this author Vincent Gnanapragasam Cambridge, United Kingdom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...