Urinary mRNA biomarker panel for the detection of urothelial carcinoma

// Virginia Urquidi 1 , Mandy Netherton 1 , Evan Gomes-Giacoia 1 , Daniel Serie 2 , Jeanette Eckel-Passow 3 , Charles J. Rosser 4 , Steve Goodison 2, 5 1 Cancer Research Institute, MD Anderson Cancer Center, Orlando, FL, USA 2 Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA 3 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA 4 University of Hawaii Cancer Center, Honolulu, HI, USA 5 Department of Urology, Mayo Clinic, Jacksonville, FL, USA Correspondence to: Steve Goodison, email: goodison.steven@mayo.edu Keywords: diagnostic biomarkers, bladder cancer, multiplex, urinalysis, non-invasive Received: March 21, 2016     Accepted: April 28, 2016     Published: May 25, 2016 ABSTRACT The early detection of bladder cancer is important as the disease has a high rate of recurrence and progression. The development of accurate, non-invasive urinary assays would greatly facilitate detection. In previous studies, we have reported the discovery and initial validation of mRNA biomarkers that may be applicable in this context. In this study, we evaluated the diagnostic performance of proposed molecular signatures in an independent cohort. Forty-four mRNA transcripts were monitored blindly in urine samples obtained from a cohort of 196 subjects with known bladder disease status (89 with active BCa) using quantitative real-time PCR (RT-PCR). Statistical analyses defined associations of individual biomarkers with clinical data and the performance of predictive multivariate models was assessed using ROC curves. The majority of the candidate mRNA targets were confirmed as being associated with the presence of BCa over other clinical variables. Multivariate models identified an optimal 18-gene diagnostic signature that predicted the presence of BCa with a sensitivity of 85% and a specificity of 88% (AUC 0.935). Analysis of mRNA signatures in naturally micturated urine samples can provide valuable information for the evaluation of patients under investigation for BCa. Additional refinement and validation of promising multi-target signatures will support the development of accurate assays for the non-invasive detection and monitoring of BCa.