MP29-03 TET3, HELLS, TOP2A AND ATAD2 ARE NOVEL INDEPENDENT PROGNOSTIC MARKERS IN ADVANCED RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2014MP29-03 TET3, HELLS, TOP2A AND ATAD2 ARE NOVEL INDEPENDENT PROGNOSTIC MARKERS IN ADVANCED RENAL CELL CARCINOMA Dong Chen, Matthias Maruschke, Rainer Riesenberg, Wolfgang Zimmermann, Christian. G. Stief, and Alexander Buchner Dong ChenDong Chen More articles by this author , Matthias MaruschkeMatthias Maruschke More articles by this author , Rainer RiesenbergRainer Riesenberg More articles by this author , Wolfgang ZimmermannWolfgang Zimmermann More articles by this author , Christian. G. StiefChristian. G. Stief More articles by this author , and Alexander BuchnerAlexander Buchner More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.745AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A significant proportion of patients with renal cell carcinoma (RCC) will have metastases at first diagnosis or develop metastases during the course of their disease. Individual risk stratification based on reliable prognostic markers is needed to allow a personalized therapeutic strategy. The aim of our study was to screen for promising prognostic markers using a novel filtering approach, based on genes that are subsequently up-regulated in primary tumors and metastases. Therefore, we created microarray expression data from RCC patients including normal kidney tissue, primary tumors and metastases. The best candidate genes were validated using RT-PCR. METHODS Tissue samples from normal renal tissue (n=14), primary tumor (14x G1, 14x G3) and metastases (n=32) were collected from patients with clear-cell RCC. Follow-up data were available from all patients. The tissue was snap-frozen immediately after surgery, and total RNA was isolated. Expression profiles were created using oligonucleotide microarrays (GeneChip HG U133 Plus 2.0, Affymetrix). For analysis of expression data, the dChip 2010 software was used. Gene expression was compared between normal kidney, primary tumor and metastases. Furthermore, a significance test was applied. In all filtered genes, univariate survival analysis was carried out (Kaplan-Meier method, log-rank test). Significant genes were further analyzed using multivariate Cox regression models. The best candidate markers were further validated in an independent cohort of 52 primary tumors using quantitative RT-PCR and immunohistochemistry. RESULTS Expression analysis revealed that in 59 probe sets there was increased expression in primary RCC compared with normal kidney, and also in metastases compared with primary tumors. In uni- or multivariate survival analysis, 15 of these probe sets were significant. Undefined genes (C1orf216 and Hs.133294.1) and genes with very low mRNA level in RT-PCR (NDC80, GOLSYN, DTL, and BUB1B) were excluded. Eight genes (TOP2A, SFN, CENPF, AMPD3, ATAD2, AURKA, HELLS and TET3) were afterwards validated by quantitative RT-PCR. Survival analysis in an independent cohort of 52 primary RCCs showed that TOP2A (HR=4.4, p=0.004), TET3 (HR=2.9, p=0.031), HELLS (HR=3.6, p=0.007), and ATAD2 (HR=3.8, p=0.014) represent independent predictors for RCC patients. TOP2A IHC results support the RT-PCR findings. CONCLUSIONS High expression of TET3, HELLS, TOP2A, and ATAD2 are independent predictors of poor outcome in RCC patients and may be used for individual risk-adapted therapy in the future. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e305 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Dong Chen More articles by this author Matthias Maruschke More articles by this author Rainer Riesenberg More articles by this author Wolfgang Zimmermann More articles by this author Christian. G. Stief More articles by this author Alexander Buchner More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...