MP68-04 A FIVE—GENE DNA—METHYLATION BIOMARKER PANEL SENSITIVELY DETECTS BLADDER CANCER AND DISCRIMINATES BETWEEN HIGH—GRADE AND LOW—GRADE DISEASE IN VOIDED URINE

You have accessJournal of UrologyBladder Cancer: Basic Research IV1 Apr 2015MP68-04 A FIVE—GENE DNA—METHYLATION BIOMARKER PANEL SENSITIVELY DETECTS BLADDER CANCER AND DISCRIMINATES BETWEEN HIGH—GRADE AND LOW—GRADE DISEASE IN VOIDED URINE Thomas Hermanns, Ekaterina Olkhov-Mitsel, Andrea Savio, Bethany Gill, Jenna Sykes, Bimal Bhindi, Tristan Juvet, Cynthia Kuk, Aidan Noon, Ricardo Rendon, David Waltregny, Theodorus H. van der Kwast, Antonio Finelli, Neil E. Fleshner, Kirk Lo, Bharati Bapat, and Alexandre R. Zlotta Thomas HermannsThomas Hermanns More articles by this author , Ekaterina Olkhov-MitselEkaterina Olkhov-Mitsel More articles by this author , Andrea SavioAndrea Savio More articles by this author , Bethany GillBethany Gill More articles by this author , Jenna SykesJenna Sykes More articles by this author , Bimal BhindiBimal Bhindi More articles by this author , Tristan JuvetTristan Juvet More articles by this author , Cynthia KukCynthia Kuk More articles by this author , Aidan NoonAidan Noon More articles by this author , Ricardo RendonRicardo Rendon More articles by this author , David WaltregnyDavid Waltregny More articles by this author , Theodorus H. van der KwastTheodorus H. van der Kwast More articles by this author , Antonio FinelliAntonio Finelli More articles by this author , Neil E. FleshnerNeil E. Fleshner More articles by this author , Kirk LoKirk Lo More articles by this author , Bharati BapatBharati Bapat More articles by this author , and Alexandre R. ZlottaAlexandre R. Zlotta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2466AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Voided urine provides an excellent source of exfoliated cells from the bladder and an ideal medium for detection of bladder cancer (BC) biomarkers. Using two different genome−wide methylation−array profiling platforms in Toronto, CA and Liège, BE, several deferentially methylated genes (TWIST1, NID2, RunX3, Gata4, FoxE1) from low grade (LG) vs. high grade (HG) BC were commonly identified. We investigated methylation of the five genes to non−invasively identify BC in voided urine and discriminate between LG and HG BC METHODS Voided urine from patients with histologically proven LG (n=59) and HG BC (n=64) as well as from BC−free controls (noBC, n=59) was collected. DNA extracted from the urinary cell pellets was analyzed using a highly sensitive, quantitative methylation specific assay (MethyLight) to examine the methylation status of selected candidate genes. Methylation levels (percent methylation reference, PMR) for each sample were obtained from averaging duplicate runs. Associations between PMR and diagnosis of HG vs. LG disease vs. noBC, BC overall vs. noBC and HG vs. LG were performed using the Kruskal−Wallis test or the Mann−Whitney U−test. Univariate and multivariable logistic regression models were used to create ROC curves to evaluate individual biomarker discrimination and combined discrimination, respectively. The Akaike information criterion was used to determine which biomarkers and clinical variables were necessary to include in the final model. RESULTS The median PMRs for each gene were significantly different for HG, LG and noBC (RunX3: p=.0011, all others: p<0.001). The PMRs were significantly higher in BC cases compared to noBC cases for all genes (all p<0.001) and for HG compared to LG BC cases (RunX3: p=.0011, all others: p<0.001). The AUC to predict BC overall was.75 (95%CI:.69−.82) for TWIST1,.75 (.68−.82) for NID2,.70 (.63−.77) for RUNX3,.75 (.68−.81) for Gata4 and.63 (.58−.68) for FoxE1. For the prediction of HG BC the AUC was.72 (.65−.80) for TWIST1,.72 (.63−.81) for NID2,.57 (.49−.66) for RUNX3,.67 (.59−.74) for Gata4 and.68 (.61−.76) for FoxE1. The final model for BC included TWIST, RunX3 Gata 4 and age (AUC:.87 (.81−.92)). The final model for HG versus LG BC included TWIST, Fox E1, NID2 and age (AUC:.83 (.75−.90)). CONCLUSIONS A combination of five epigenetic markers (TWIST1, RunX3, FoxE1, Gata4, NID2) is a very promising non−invasive tool for sensitive and specific BC detection and prognostication. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e859 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Thomas Hermanns More articles by this author Ekaterina Olkhov-Mitsel More articles by this author Andrea Savio More articles by this author Bethany Gill More articles by this author Jenna Sykes More articles by this author Bimal Bhindi More articles by this author Tristan Juvet More articles by this author Cynthia Kuk More articles by this author Aidan Noon More articles by this author Ricardo Rendon More articles by this author David Waltregny More articles by this author Theodorus H. van der Kwast More articles by this author Antonio Finelli More articles by this author Neil E. Fleshner More articles by this author Kirk Lo More articles by this author Bharati Bapat More articles by this author Alexandre R. Zlotta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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