You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 2016MP02-03 NEXT-GENERATION SEQUENCING REVEALS TRANSCRIPT CLUSTERS WITH PROGNOSTIC POTENTIAL FOR PROSTATE CANCER Friedemann Horn, Sabina Christ-Breulmann, Sven-Holger Puppel, Tilo Buschmann, Kristin Reiche, Michael Specht, Catharina Bertram, Maik Friedrich, Stefanie Binder, Conny Blumert, Jörg Hackermüller, Markus Kreuz, Markus Löffler, Marieta I. Toma, Michael Muders, Gustavo B. Baretton, Michael Fröhner, Susanne Füssel, and Manfred Wirth Friedemann HornFriedemann Horn More articles by this author , Sabina Christ-BreulmannSabina Christ-Breulmann More articles by this author , Sven-Holger PuppelSven-Holger Puppel More articles by this author , Tilo BuschmannTilo Buschmann More articles by this author , Kristin ReicheKristin Reiche More articles by this author , Michael SpechtMichael Specht More articles by this author , Catharina BertramCatharina Bertram More articles by this author , Maik FriedrichMaik Friedrich More articles by this author , Stefanie BinderStefanie Binder More articles by this author , Conny BlumertConny Blumert More articles by this author , Jörg HackermüllerJörg Hackermüller More articles by this author , Markus KreuzMarkus Kreuz More articles by this author , Markus LöfflerMarkus Löffler More articles by this author , Marieta I. TomaMarieta I. Toma More articles by this author , Michael MudersMichael Muders More articles by this author , Gustavo B. BarettonGustavo B. Baretton More articles by this author , Michael FröhnerMichael Fröhner More articles by this author , Susanne FüsselSusanne Füssel More articles by this author , and Manfred WirthManfred Wirth More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1875AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) is the most common malignant tumor in men. Although first assays for risk assessment are available, the choice of whether or not to use interventional treatment for low-risk disease remains difficult. The Fraunhofer-led RIBOLUTION consortium conducted an unbiased transcriptome-wide expression study in PCa tumor tissues. METHODS Using strand-specific, paired-end long-RNA next-generation sequencing (NGS) and microarray studies, we analysed the transcriptomes of prostate tumor and tumor-free samples. Fresh frozen tissues were obtained from radical prostatectomies of PCa patients with a follow-up of at least 7 years. The cohort was stratified to contain distinct risk groups with respect to Gleason score, lymph node metastases, and survival. RNA was isolated from cryosections, quality-controlled for tumor cell contents. 64 samples were subjected to NGS at a depth of 200 million reads per sample. Subsequently, 256 prostate samples were studied using customized microarrays covering transcripts differentially expressed in the sequencing cohort as well as all RNAs annotated in public databases. To retrieve prognostic biomarker signatures, the data obtained were analysed using a correlational clustering and self organizing maps (SOM) approach. RESULTS We identified high numbers of transcripts that are differentially expressed between the PCa risk groups and defined several clusters of transcripts that exhibit strong prognostic potential. Kaplan-Meier analysis showed a clear separation of the survival and death of disease groups. A biomarker signature generated from these clusters yielded an area under the ROC curve (AUC) value of 0.80 for specificity and sensitivity. As a comparison, the transcripts used for two commercially available prognostic PCa tests yielded AUC values of 0.67 and 0.66, respectively, in our cohort. To study the pathway correlation of the clusters, we knocked down the androgen receptor, STAT3, and MAP kinase pathways by RNA interference in PCa cell lines. The results demonstrate that the transcript clusters with prognostic potential relate to distinct biological networks. CONCLUSIONS Our study reveals clusters of RNA transcripts from PCa tumor tissue that exhibit strong prognostic potential. By combining these clusters, a biomarker signature was generated that discriminated survival from PCa-specific death with high specificity and sensitivity. This signature might be the basis for the development of a prognostic test for PCa. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e10 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Friedemann Horn More articles by this author Sabina Christ-Breulmann More articles by this author Sven-Holger Puppel More articles by this author Tilo Buschmann More articles by this author Kristin Reiche More articles by this author Michael Specht More articles by this author Catharina Bertram More articles by this author Maik Friedrich More articles by this author Stefanie Binder More articles by this author Conny Blumert More articles by this author Jörg Hackermüller More articles by this author Markus Kreuz More articles by this author Markus Löffler More articles by this author Marieta I. Toma More articles by this author Michael Muders More articles by this author Gustavo B. Baretton More articles by this author Michael Fröhner More articles by this author Susanne Füssel More articles by this author Manfred Wirth More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...