1287 METHYLATION OF A NOVEL PANEL OF TUMOR SUPPRESSOR GENES ALLOWS NON-INVASIVE DIAGNOSIS AND PROGNOSIS IN BLADDER CANCER: A TWO CENTER PROSPECTIVE STUDY

Abstract

You have accessJournal of UrologyBladder Cancer: Detection & Screening1 Apr 20131287 METHYLATION OF A NOVEL PANEL OF TUMOR SUPPRESSOR GENES ALLOWS NON-INVASIVE DIAGNOSIS AND PROGNOSIS IN BLADDER CANCER: A TWO CENTER PROSPECTIVE STUDY Rodrigo Garcia-Baquero, Patricia Puerta, Manuel Beltran, Miguel Alvarez, Raquel Sacristan, Jose Luis Ossorio, and Marta Sanchez-Carbayo Rodrigo Garcia-BaqueroRodrigo Garcia-Baquero Madrid, Spain More articles by this author , Patricia PuertaPatricia Puerta Madrid, Spain More articles by this author , Manuel BeltranManuel Beltran Cadiz, Spain More articles by this author , Miguel AlvarezMiguel Alvarez Oviedo, Spain More articles by this author , Raquel SacristanRaquel Sacristan Oviedo, Spain More articles by this author , Jose Luis OssorioJose Luis Ossorio Cadiz, Spain More articles by this author , and Marta Sanchez-CarbayoMarta Sanchez-Carbayo Madrid, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2641AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Changes in DNA methylation of tumor suppressor genes (TSGs) occurring early in carcinogenesis, represent potential indicators for cancer detection and disease evolution. Our aim was to examine the biomarker role of the methylation of TSGs in bladder cancer. METHODS Methylation of 18 TSGs was evaluated in bladder cancer cells (n=14), fresh-frozen primary bladder tumors (n=61), and two prospective independent sets of urines (training, n=120; and validation, n=128) using methylation-specific multiplex ligation-dependent probe amplification assays (MS-MLPA). Diagnostic performance was evaluated using Receiver Operating Curves. Recurrence, progression, and disease-specific survival were analyzed using univariate and multivariate Cox models. RESULTS PRDM2, HLTF, ID4, DLC1, BNIP3, H2AFX, CACNA1G, TGIF, and CACNA1A were discovered methylated in bladder cancer. In tumors, RUNX3 (p=0.026), TWIST1 (p=0.009), SFRP4 (p=0.002) and CCND2 (p= 0.027) methylation correlated to stage. Univariate analyses indicated prognostic associations for recurrence (DLC1, SFRP5, H2AFX, CACNA1G), progression (DLC1, SFRP5, CACNA1G), disease-specific (PRDM2, DLC1, SFRP5, CACNA1G, and TIMP3), and overall survival (SFRP5 and TIMP3), remaining independent prognosticators in multivariate analyses for recurrence (SFRP5, H2AFX), progression (CACNA1G), and disease-specific survival (SFRP5). CCND2, SCGB3A1 and RUNX3 were the most frequently methylated TSGs in both urinary sets. ROC analyses revealed significant diagnostic accuracies for RUNX3 in both series. Using univariate and multivariate analyses, CACNA1A methylation correlated to recurrence in the training set, while PRDM2 with recurrence and BNIP3 with disease-specific survival in the validation set. CONCLUSIONS In tumors, TSGs methylation allowed histopathologic and outcome stratification. Urinary methylation offered non-invasive utility not only for diagnosis but also for prognosis. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e526 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rodrigo Garcia-Baquero Madrid, Spain More articles by this author Patricia Puerta Madrid, Spain More articles by this author Manuel Beltran Cadiz, Spain More articles by this author Miguel Alvarez Oviedo, Spain More articles by this author Raquel Sacristan Oviedo, Spain More articles by this author Jose Luis Ossorio Cadiz, Spain More articles by this author Marta Sanchez-Carbayo Madrid, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...