602 EPITHELIAL-MESENCHYMAL TRANSITION (EMT) IN METASTATIC RENAL CELL CARCINOMA AND PROGNOSTIC RELEVANCE OF INVOLVED GENES

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research (IV)1 Apr 2013602 EPITHELIAL-MESENCHYMAL TRANSITION (EMT) IN METASTATIC RENAL CELL CARCINOMA AND PROGNOSTIC RELEVANCE OF INVOLVED GENES Alexander Buchner, Rainer Riesenberg, Heike Pohla, Wolfgang Zimmermann, Christian Stief, and Dong Chen Alexander BuchnerAlexander Buchner Munich, Germany More articles by this author , Rainer RiesenbergRainer Riesenberg Munich, Germany More articles by this author , Heike PohlaHeike Pohla Munich, Germany More articles by this author , Wolfgang ZimmermannWolfgang Zimmermann Munich, Germany More articles by this author , Christian StiefChristian Stief Munich, Germany More articles by this author , and Dong ChenDong Chen Munich, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.153AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Epithelial-mesenchymal transition (EMT) is a phenotype change that occurs in tumorigenesis and tumor progression. It is characterized by several well-established changes in gene expression, leading to reduced intercellular adhesion and increased cell motility and invasiveness. There is a strong association between EMT and cancer stem cell biology. Until now, little is known about EMT and cancer stem cells in renal cell carcinoma (RCC). The objective of this study was to analyze the expression of EMT-related genes in metastatic RCC, and thereby the identification of new prognostic markers and potential novel therapy targets. METHODS A total of 112 tissue samples from 82 patients with metastatic RCC (normal kidney tissue n=19, primary tumor n=55, metastases n=38) were snap-frozen immediately after surgery. Total RNA was extracted and tested for integrity. Quantitative RT-PCR was performed using primers for a panel of 15 genes associated with EMT and with cancer stem cell biology. For selected genes, expression was validated using immunohistochemistry and Western blot. Cancer-specific survival was analyzed using log rank test and multivariate Cox regression models. RESULTS Median follow-up time was 54 months (maximum 197 months). Significantly changed expression of several EMT-related genes was observed in RCC tissue, e.g. downregulation of epithelial adhesion molecule E-cadherin in primary tumor and metastases compared to normal kidney tissue. There was a significant increase of CXCR4 (a chemokine receptor, known as a cancer stem cell marker in several tumors) during tumor progression (metastases > primary tumour > normal kidney tissue, p<0.001). Univariate analysis showed a significantly better outcome in patients with decreased expression of CXCR4 (p<0.001), TWIST (p=0.029) and MMP2 (p=0.045) and increased expression of E-cadherin (0.048), CXCR7 (p=0.009), CXCL12 (p=0.047), WWTR1 (p=0.006), and YAP1 (p=0.008). In multivariate analysis, MMP2 and E-cadherin were independent prognostic markers for cancer-specific survival (p=0.034 and p=0.020, respectively). CONCLUSIONS Our results show that there is strong evidence for EMT in metastatic RCC. The putative cancer stem cell marker CXCR4 is increased in primary tumors and metastases. Some of the observed gene expression changes might be useful for the development of novel therapeutic strategies, e.g. inhibition of CXCR4. MMP2 and E-cadherin were independent outcome predictors and can be used to optimize the individual risk stratification of RCC patients. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e246 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Buchner Munich, Germany More articles by this author Rainer Riesenberg Munich, Germany More articles by this author Heike Pohla Munich, Germany More articles by this author Wolfgang Zimmermann Munich, Germany More articles by this author Christian Stief Munich, Germany More articles by this author Dong Chen Munich, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...