title: A urinary microRNA signature can predict the presence of bladder urothelial carcinoma in patients undergoing surveillance.
abstract: BACKGROUND
  The objective of this study was to determine whether microRNA (miRNA) profiling of urine could identify the presence of urothelial carcinoma of the bladder (UCB) and to compare its performance characteristics to that of cystoscopy.
  
  
  METHODS
  In the discovery cohort we screened 81 patients, which included 21 benign controls, 30 non-recurrers and 30 patients with active cancer (recurrers), using a panel of 12 miRNAs. Data analysis was performed using a machine learning approach of a Support Vector Machine classifier with a Student's t-test feature selection procedure. This was trained using a three-fold cross validation approach and performance was measured using the area under the receiver operator characteristic curve (AUC). The miRNA signature was validated in an independent cohort of a further 50 patients.
  
  
  RESULTS
  The best predictor to distinguish patients with UCB from non-recurrers was achieved using a combination of six miRNAs (AUC=0.85). This validated in an independent cohort (AUC=0.74) and detected UCB with a high sensitivity (88%) and sufficient specificity (48%) with all significant cancers identified. The performance of the classifier was best in detecting clinically significant disease such as presence of T1 Stage disease (AUC=0.92) and high-volume disease (AUC=0.81). Cystoscopy rates in the validation cohort would have been reduced by 30%.
  
  
  CONCLUSIONS
  Urinary profiling using this panel of miRNAs shows promise for detection of tumour recurrence in the surveillance of UCB. Such a panel may be useful in reducing the morbidity and costs associated with cystoscopic surveillance, and now merits prospective evaluation.
authors.affiliation: Department of Surgery, Division of Urology, Royal Melbourne Hospital, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Sapre
authors.affiliation: NICTA Victoria Research Laboratory, Department of Electronic Engineering, University of Melbourne, Melbourne, Victoria, Australia.|Department of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia.|Centre for Neural Engineering, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Geoff
authors.initials: G
authors.lastname: Macintyre
authors.affiliation: Department of Surgery, Division of Urology, Royal Melbourne Hospital, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Clarkson
authors.affiliation: NICTA Victoria Research Laboratory, Department of Electronic Engineering, University of Melbourne, Melbourne, Victoria, Australia.|Department of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia.|Centre for Neural Engineering, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Haroon
authors.initials: H
authors.lastname: Naeem
authors.affiliation: NICTA Victoria Research Laboratory, Department of Electronic Engineering, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Marek
authors.initials: M
authors.lastname: Cmero
authors.affiliation: NICTA Victoria Research Laboratory, Department of Electronic Engineering, University of Melbourne, Melbourne, Victoria, Australia.|Department of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia.|Centre for Neural Engineering, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Kowalczyk
authors.affiliation: Department of Surgery, Division of Urology, Royal Melbourne Hospital, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Anderson
authors.affiliation: Department of Surgery, Division of Urology, Royal Melbourne Hospital, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Costello
authors.affiliation: Department of Surgery, Division of Urology, Royal Melbourne Hospital, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Niall M
authors.initials: NM
authors.lastname: Corcoran
authors.affiliation: Department of Surgery, Division of Urology, Royal Melbourne Hospital, The University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hovens
mesh_terms: D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D015331:Cohort Studies; D003558:Cystoscopy / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000652:urine*; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
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