title: Urinary mRNA biomarker panel for the detection of urothelial carcinoma.
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.
authors.affiliation: Cancer Research Institute, MD Anderson Cancer Center, Orlando, FL, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Urquidi
authors.affiliation: Cancer Research Institute, MD Anderson Cancer Center, Orlando, FL, USA.
authors.forename: Mandy
authors.initials: M
authors.lastname: Netherton
authors.affiliation: Cancer Research Institute, MD Anderson Cancer Center, Orlando, FL, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Gomes-Giacoia
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Serie
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Eckel-Passow
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.|Department of Urology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Goodison
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine*; D002277:Carcinoma / Q000175:diagnosis* / Q000652:urine*; D016022:Case-Control Studies; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D015999:Multivariate Analysis; D012372:ROC Curve; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D035683:MicroRNAs
keywords: bladder cancer; diagnostic biomarkers; multiplex; non-invasive; urinalysis