MP68-18 MOLECULAR ANALYSIS OF UROTHELIAL TUMORS IN PATIENTS WITH AND WITHOUT METASTASIS STRATIFIED BY T STAGE

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research IV1 Apr 2015MP68-18 MOLECULAR ANALYSIS OF UROTHELIAL TUMORS IN PATIENTS WITH AND WITHOUT METASTASIS STRATIFIED BY T STAGE Tom Sanford, Christopher Welty, Max Meng, and Sima Porten Tom SanfordTom Sanford More articles by this author , Christopher WeltyChristopher Welty More articles by this author , Max MengMax Meng More articles by this author , and Sima PortenSima Porten More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2480AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The Cancer Genome Atlas (TCGA) project recently published a global analysis of urothelial carcinoma that provided insight into the pathogenesis of urothelial carcinoma. However, the molecular correlates to clinical parameters associated with patient outcomes have yet to be fully characterized. In this study, we use RNA-seq data from TCGA to evaluate expression changes in the primary tumor of patients with and without lymph node metastasis stratified by T stage. METHODS Raw count RNA-seq data was downloaded from the Broad Institute Firehose Pipeline (http://gdac.broadinstitute.org/) for all patients with associated clinical data. Pathology reports were reviewed and we recorded the T stage, N stage, and number of lymph nodes examined. Raw counts were imported into R v 3.12 and analyzed with the edgeR package. Data was stratified according to T stage (T2, T3, T4) for further analysis and all patients with negative lymph nodes who had less than 15 nodes examined were excluded. Exploratory data analysis was performed using Minus Average (MA) plots. Differential gene expression was performed evaluating differences between the primary tumors of lymph node positive and lymph node negative patients stratified by T stage. Pathway analysis was performed using iPathwayGuide. RESULTS There were a total of 176 patients with pathologic information. A total of 106 patients met inclusion criteria: 23 T2 (8 N+, 15 N-), 64 T3 (30 N+, 34 N-), 19 T4 (15 N+, 4 N-). MAplots comparing N+ and N- patients showed increasing variability with increasing T stage (Figure 1). There were a total of 4, 744, and 84 differentially expressed genes for T2, T3, and T4 tumors, respectively (p<0.01, q<0.05). There were only 8 differentially expressed genes that overlapped between T3 and T4 tumors; no genes overlapped all three groups. Pathway analysis showed involvement of PIK3-Akt pathway in T2 tumors, the MAPK signaling pathway in T3 tumors, and GnRH signaling in T4 tumors. CONCLUSIONS There appears to be an increase in differential gene expression between tumors that have the biological capacity to spread to lymph nodes and those that do not, as T stage increases. Each T stage is associated with enrichment in unique pathways. This may shed light on the biologic heterogeneity in bladder cancer and potential differential pathways to metastasis. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e865 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tom Sanford More articles by this author Christopher Welty More articles by this author Max Meng More articles by this author Sima Porten More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...