A urinary microRNA signature can predict the presence of bladder urothelial carcinoma in patients undergoing surveillance

• Published in: British journal of cancer 2016-02, Vol.114 (4), p.454-462
• Main Authors: Sapre, Nikhil, Macintyre, Geoff, Clarkson, Michael, Naeem, Haroon, Cmero, Marek, Kowalczyk, Adam, Anderson, Paul D, Costello, Anthony J, Corcoran, Niall M, Hovens, Christopher M
• Format: Article
• Language: English
• Subjects: 631/337/384/331; 692/699/67/1857; 692/699/67/589/1336; Biomarkers, Tumor - urine; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Cohort Studies; Cystoscopy - methods; Drug Resistance; Epidemiology; Humans; MicroRNAs - urine; Molecular Diagnostics; Molecular Medicine; Oncology; Prognosis; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - urine
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2015.472

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.