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Expression and Prognostic Significance of a Comprehensive Epithelial-Mesenchymal Transition Gene Set in Renal Cell Carcinoma

2013; Lippincott Williams & Wilkins; Volume: 191; Issue: 2 Linguagem: Inglês

10.1016/j.juro.2013.08.052

1527-3792

Dong Chen, Maximilian Gassenmaier, Matthias Maruschke, Rainer Riesenberg, Heike Pohla, Christian G. Stief, Wolfgang Zimmermann, Alexander Büchner,

Ferroptosis and cancer prognosis

No AccessJournal of UrologyInvestigative Urology1 Feb 2014Expression and Prognostic Significance of a Comprehensive Epithelial-Mesenchymal Transition Gene Set in Renal Cell Carcinoma Dong Chen, Maximilian Gassenmaier, Matthias Maruschke, Rainer Riesenberg, Heike Pohla, Christian G. Stief, Wolfgang Zimmermann, and Alexander Buchner Dong ChenDong Chen Department of Urology, University Hospital, Munich, Germany Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China , Maximilian GassenmaierMaximilian Gassenmaier Tumor Immunology Laboratory, LIFE Center, Munich, Germany , Matthias MaruschkeMatthias Maruschke Department of Urology, University of Rostock, Rostock, Germany , Rainer RiesenbergRainer Riesenberg Tumor Immunology Laboratory, LIFE Center, Munich, Germany , Heike PohlaHeike Pohla Tumor Immunology Laboratory, LIFE Center, Munich, Germany , Christian G. StiefChristian G. Stief Department of Urology, University Hospital, Munich, Germany , Wolfgang ZimmermannWolfgang Zimmermann Tumor Immunology Laboratory, LIFE Center, Munich, Germany , and Alexander BuchnerAlexander Buchner Ludwig-Maximilians-University, Munich, Germany View All Author Informationhttps://doi.org/10.1016/j.juro.2013.08.052AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Epithelial-mesenchymal transition enhances tumor cell motility and has a critical role in invasion and metastasis in a number of carcinomas. A set of transcription factors acts as a master regulator of the epithelial-mesenchymal transition process. To our knowledge it is unknown whether epithelial-mesenchymal transition is important for clear cell renal cell carcinoma progression. Therefore, we comprehensively assessed mRNA levels of epithelial-mesenchymal transition associated genes in renal cell carcinoma as well as their prognostic relevance. Materials and Methods: We determined the expression of a set of 46 epithelial-mesenchymal transition related genes by oligonucleotide microarray and gene set enrichment analyses using RNA from 14 samples each of normal kidneys, and G1 and G3 primary renal cell carcinomas. Expression of select epithelial-mesenchymal transition genes was validated by real-time polymerase chain reaction in normal kidneys, primary renal cell carcinomas and metastases in an independent cohort of 112 patients. Results were combined with followup data for survival analysis. Results: The epithelial-mesenchymal transition gene set was preferentially expressed in primary renal cell carcinoma compared to normal tissue (false discovery rate 0.01). No difference was found between G1 and G3 tumors. Quantitative reverse transcriptase-polymerase chain reaction revealed down-regulation of critical epithelial-mesenchymal transition genes such as CDH2 and ZEB1 in metastases, suggesting epithelial-mesenchymal transition reversal during metastasis. Kaplan-Meier analysis demonstrated a better outcome in patients with low CXCR4, vimentin, fibronectin and TWIST1 mRNA levels. Multivariate analyses revealed that CXCR4 and VIM up-regulation represents an independent prognostic marker for poor cancer specific survival in patients with renal cell carcinoma. Conclusions: Taken together, our data provide strong evidence that epithelial-mesenchymal transition occurs in renal cell carcinoma. Thus, interference with epithelial-mesenchymal transition in renal cell carcinoma might represent a future therapeutic option. References 1 : Epithelial-mesenchymal transitions in development and disease. Cell2009; 139: 871. Google Scholar 2 : EMT as the ultimate survival mechanism of cancer cells. 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Google Scholar © 2014FiguresReferencesRelatedDetailsCited byAtala A (2018) Re: A miR-192-EGR1-HOXB9 Regulatory Network Controls the Angiogenic Switch in CancerJournal of Urology, VOL. 197, NO. 4, (1002-1003), Online publication date: 1-Apr-2017.Boguslawska J, Kedzierska H, Poplawski P, Rybicka B, Tanski Z and Piekielko-Witkowska A (2018) Expression of Genes Involved in Cellular Adhesion and Extracellular Matrix Remodeling Correlates with Poor Survival of Patients with Renal CancerJournal of Urology, VOL. 195, NO. 6, (1892-1902), Online publication date: 1-Jun-2016.Atala A (2016) Re: Human Schlafen 5 (SLFN5) is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma CellsJournal of Urology, VOL. 195, NO. 4 Part 1, (1169-1169), Online publication date: 1-Apr-2016.Atala A (2018) Re: Targeted Fibrillar Nanocarbon RNAi Treatment of Acute Kidney InjuryJournal of Urology, VOL. 196, NO. 4, (1313-1314), Online publication date: 1-Oct-2016.Laguna M (2018) Re: ClearCode34: A Prognostic Risk Predictor for Localized Clear Cell Renal Cell CarcinomaJournal of Urology, VOL. 193, NO. 1, (71-72), Online publication date: 1-Jan-2015. Volume 191Issue 2February 2014Page: 479-486Supplementary Materials Advertisement Copyright & Permissions© 2014Keywordsgene expressionkidneyclear cellprognosiscarcinomaepithelial-mesenchymal transitionAcknowledgmentsDr. Matthias May provided statistical advice. Dr. Gerald Assmann evaluated kidney tissues.MetricsAuthor Information Dong Chen Department of Urology, University Hospital, Munich, Germany Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China More articles by this author Maximilian Gassenmaier Tumor Immunology Laboratory, LIFE Center, Munich, Germany More articles by this author Matthias Maruschke Department of Urology, University of Rostock, Rostock, Germany More articles by this author Rainer Riesenberg Tumor Immunology Laboratory, LIFE Center, Munich, Germany More articles by this author Heike Pohla Tumor Immunology Laboratory, LIFE Center, Munich, Germany More articles by this author Christian G. Stief Department of Urology, University Hospital, Munich, Germany More articles by this author Wolfgang Zimmermann Tumor Immunology Laboratory, LIFE Center, Munich, Germany Equal study contribution. More articles by this author Alexander Buchner Ludwig-Maximilians-University, Munich, Germany Equal study contribution. More articles by this author Expand All Advertisement PDF downloadLoading ...