1699 IDENTIFYING NOVEL DNA METHYLATION MARKERS TO MONITOR BLADDER CANCER RECURRENCE IN URINE SEDIMENTS FROM TURBT PATIENTS (2013)

You have accessJournal of UrologyBladder Cancer: Superficial (I)1 Apr 20131699 IDENTIFYING NOVEL DNA METHYLATION MARKERS TO MONITOR BLADDER CANCER RECURRENCE IN URINE SEDIMENTS FROM TURBT PATIENTS Andre Luis de Castro Abreu, Sheng-Fang Su, Kimberly Siegmund, Yvonne Tsai, Yoshitomo Chihara, Eila Skinner, Sia Daneshmand, Peter A. Jones, and Gangning Liang Andre Luis de Castro AbreuAndre Luis de Castro Abreu Los Angeles, CA , Sheng-Fang SuSheng-Fang Su Los Angeles, CA , Kimberly SiegmundKimberly Siegmund Los Angeles, CA , Yvonne TsaiYvonne Tsai Los Angeles, CA , Yoshitomo ChiharaYoshitomo Chihara Los Angeles, CA , Eila SkinnerEila Skinner Los Angeles, CA , Sia DaneshmandSia Daneshmand Los Angeles, CA , Peter A. JonesPeter A. Jones Los Angeles, CA , and Gangning LiangGangning Liang Los Angeles, CA View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.3009AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The high risk of recurrence in patients following transurethral resection of non-muscle invasive bladder tumor (TURBT) requires lifelong maintenance treatment and surveillance, currently by cytology and cystoscopic examination which creates a substantial financial burden. Aberrant DNA methylation occurs early during tumorigenesis and is present in premalignant lesions, and therefore, DNA methylation analysis of cancer-related genes serve as promising biomarkers. However, urine-based DNA methylation analysis to monitor TURBT patients longitudinally, which also may allow non-invasive recurrent tumor detection before clinical diagnosis, has not yet been well established thus far. METHODS Using pyrosequencing, we analyzed DNA methylation levels in a panel of six methylation markers in 368 serial urine samples from 90 post-surgical patients. The sensitivity and specificity in detecting tumor recurrence were summarized by ROC curves and AUC values. The optimum combination of markers was identified using five-fold cross-validation in 29 urine samples from patients at first recurrence on study and 54 samples from the last follow-up of patients without recurrence; the combination was then validated in 23 urine samples indicating tumor and 135 recurrence-free samples. RESULTS The methylation profiles of six markers individually showed a high sensitivity and specificity in detecting tumor recurrence (all AUC≥0·9; p<0·0001). The three-marker model displayed 86% sensitivity and 89% specificity in discriminating between samples with and without recurrence, as well as 83% sensitivity and 97% specificity in a separate set of samples from the same cohort. Significantly, the sensitivity of this three-marker DNA methylation analysis was higher than that of urine cytology at the time of recurrence (90% vs 16%). Furthermore, when including the period before recurrence, the established cut-off value that indicates positive urine test by DNA methylation analysis has a higher sensitivity than cytology (62% vs 6%) and also successfully predicts the subsequent recurrence of bladder tumor in 90% of samples, compared to only 7% by cytology. CONCLUSIONS We identify a panel of markers for which methylation can be analyzed in urine to accurately detect and predict bladder tumor recurrence in TURBT patients. Given its superior sensitivity and non-invasive nature, urine-based DNA methylation analysis would be useful in follow-up visits screening for recurrence and would improve treatment strategies in clinical utility. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e699 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andre Luis de Castro Abreu Los Angeles, CA More articles by this author Sheng-Fang Su Los Angeles, CA More articles by this author Kimberly Siegmund Los Angeles, CA More articles by this author Yvonne Tsai Los Angeles, CA More articles by this author Yoshitomo Chihara Los Angeles, CA More articles by this author Eila Skinner Los Angeles, CA More articles by this author Sia Daneshmand Los Angeles, CA More articles by this author Peter A. Jones Los Angeles, CA More articles by this author Gangning Liang Los Angeles, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...