571 EXPRESSION OF PYRUVATE DEHYDROGENASE KINASE-1 (PDK-1) AND DJ-1/PARK7 IN RENAL CELL CARCINOMA (RCC) AND ITS ASSOCIATION WITH PATHOLOGY AND OUTCOME

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2010207 EXPRESSION OF PYRUVATE DEHYDROGENASE KINASE-1 (PDK-1) AND DJ-1/PARK7 IN RENAL CELL CARCINOMA (RCC) AND ITS ASSOCIATION WITH PATHOLOGY AND OUTCOME Daniel Baumunk, Uta Reichelt, Jan Ebbing, Florian Jentzmik, Kurt Miller, Martin Schostak, and Steffen Weikert Daniel BaumunkDaniel Baumunk More articles by this author , Uta ReicheltUta Reichelt More articles by this author , Jan EbbingJan Ebbing More articles by this author , Florian JentzmikFlorian Jentzmik More articles by this author , Kurt MillerKurt Miller More articles by this author , Martin SchostakMartin Schostak More articles by this author , and Steffen WeikertSteffen Weikert More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.264AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metabolic adaptations, such as increases in glucose and energy metabolism, are thought to play a pivotal role in the biology of renal cell carcinoma (RCC). Pyruvate dehydrogenase kinase-1 (PDK-1) and the pTEN regulator DJ-1/PARK7 are thought to control metabolic pathways in cancer. In this study we investigated the expression of PDK-1 and PARK in RCC. METHODS RCC tumor tissue samples and corresponding normal parenchyma specimens were obtained from 126 patients with RCC during surgical removal of the primary tumor. Expression of PDK-1 and PARK were determined on the mRNA and protein levels using quantitative RT-PCR and immunohistochemistry. Relative mRNA expression and tumor expression relative to normal tissue were determined and analyzed for associations with pathological stage and grade categories (Kruskal-Wallis ANOVA and Chi-Square test, as appropriate). Potential associations of expression with progression-free and overall survival were analyzed using Cox regression models. RESULTS PDK-1 mRNA expression was up-regulated in RCC as compared to normal tissue (p<0.001). Significant differences were observed by tumor stage (p<0.05) with a significant trend towards lower expression with increasing tumor stage (p>0.01). The expression ratio tumor/normal also showed significant differences by tumor stage with the lowest ratio observed in pT3-disease. Expression data on the mRNA level were confirmed on the protein level with the lowest protein expression determined in pT3 tumors. PDK-1 expression was not associated with Fuhrman grade. No associations were observed for PARK expression. In an exploratory analysis, the PDK-1 expression ratio tumor/normal was inversely associated with outcome after adjustment for tumor stage and grade (HR: 0.54; 95 % CI: 0.31-0.94). CONCLUSIONS PDK-1 is up-regulated in RCC, but down-regulation may be associated with progression towards an aggressive metastasizing behaviour. Our findings further data on a key role for altered glucose metabolism in the biology of RCC, in particular in tumors with an aggressive phenotype. Berlin, Germany© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e82 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.Metrics Author Information Daniel Baumunk More articles by this author Uta Reichelt More articles by this author Jan Ebbing More articles by this author Florian Jentzmik More articles by this author Kurt Miller More articles by this author Martin Schostak More articles by this author Steffen Weikert More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...