2230 VALIDATION OF THE NEW BIOMARKER MICRO-RNA-221 TO PREDICT CANCER RELATED DEATH IN HIGH-RISK PROSTATE CARCINOMA - RESULTS OF A METAANALYSIS

Abstract

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 20122230 VALIDATION OF THE NEW BIOMARKER MICRO-RNA-221 TO PREDICT CANCER RELATED DEATH IN HIGH-RISK PROSTATE CARCINOMA - RESULTS OF A METAANALYSIS Martin Spahn, Claus Jürgen, Philip Ströbel, Evelyne Lerut, Hein van Poppel, Hubertus Riedmiller, Steven Joniau, and Burkhard Kneitz Martin SpahnMartin Spahn Würzburg, Germany More articles by this author , Claus JürgenClaus Jürgen Würzburg, Germany More articles by this author , Philip StröbelPhilip Ströbel Mannheim, Germany More articles by this author , Evelyne LerutEvelyne Lerut Leuven, Belgium More articles by this author , Hein van PoppelHein van Poppel Leuven, Belgium More articles by this author , Hubertus RiedmillerHubertus Riedmiller Würzburg, Germany More articles by this author , Steven JoniauSteven Joniau Leuven, Belgium More articles by this author , and Burkhard KneitzBurkhard Kneitz Würzburg, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2406AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Emerging evidence shows that microRNAs (miR) are involved in the pathogenesis of a variety of cancers, including prostate carcinoma (PCa). Accordingly, we have recently shown that downregulation of miR-221 expression is linked to tumor progression and cancer related death in high-risk PCa patients suggesting miR-221 as a novel prognostic marker. METHODS In order to validate our initial finding, we measured relative miR-221 expression by rt-PCR in our discovery sample (128 German patients) and an independent replication sample (83 Belgian patients) with the same measurement parameters. All patients had clinical high risk PCa (defined as either PSA>20 ng/ml or cT3/cT4 or biopsy Gleason 8-10). All tumors were reviewed and re-classified by two senior uro-pathologists (P.S. and E.L.) and areas with >90% tumor content marked and macrodissected for further analysis. Multivarite Cox proportional hazards analysis were performed for both groups independently. A meta-analysis was performed for the entire cohort. RESULTS Multivariate Cox proportional hazards analyses in both samples confirmed that decreased miR-221 expression is associated with shorter times to biochemical and clinical failure as well as cancer-related death. Due to sample-specific relative miR-221 expression values , the resulting hazard ratios from the two samples are not directly comparable. We therefore normalized the miR-221 expressions from both samples to a common standard normal distribution and re-estimated hazard ratios; of note, this transformation does not affect the associations. Due to the absence of sample heterogeneity, we conducted fixed-effects meta-analyses with the normalized miR-221 hazard ratios for the different end points. The results of the meta-analyses reflect the findings of the separately analyzed samples. MiR-221 is an independant predictor for clinical failure and cancer related death in high risk PCa. CONCLUSIONS This external validation study in combination with the metaanalysis presented underlines the potential role of miR-221 as a new biomarker in high-risk Prostate cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e899-e900 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Martin Spahn Würzburg, Germany More articles by this author Claus Jürgen Würzburg, Germany More articles by this author Philip Ströbel Mannheim, Germany More articles by this author Evelyne Lerut Leuven, Belgium More articles by this author Hein van Poppel Leuven, Belgium More articles by this author Hubertus Riedmiller Würzburg, Germany More articles by this author Steven Joniau Leuven, Belgium More articles by this author Burkhard Kneitz Würzburg, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...