title: Multiplex protein signature for the detection of bladder cancer in voided urine samples.
abstract: OBJECTIVE
  Accurate urine assays for bladder cancer detection would benefit patients and health care systems. Through extensive genomic and proteomic profiling of urine components we previously identified a panel of 8 biomarkers that can facilitate the detection of bladder cancer in voided urine samples. In this study we confirmed this diagnostic molecular signature in a diverse multicenter cohort.
  
  
  METHODS
  We performed a case-control, phase II study in which we analyzed voided urine from 102 subjects with bladder cancer and 206 with varying urological disorders. The urinary concentration of 8 biomarkers (IL-8, MMP-9 and 10, PAI-1, VEGF, ANG, CA9 and APOE) was assessed by enzyme-linked immunosorbent assay. Diagnostic performance of the panel of tested biomarkers was evaluated using ROCs and descriptive statistical values, eg sensitivity and specificity.
  
  
  RESULTS
  Seven of the 8 urine biomarkers were increased in subjects with bladder cancer relative to those without bladder cancer. The 7 biomarkers were assessed in a new model, which had an AUROC of 0.88 (95% CI 0.84-0.93), and 74% sensitivity and 90% specificity. In contrast, the sensitivity of voided urine cytology and the UroVysion® cytogenetic test in this cohort was 39% and 54%, respectively. Study limitations include analysis performed on banked urine samples and the lack of voided urine cytology and cytogenetic test data on controls.
  
  
  CONCLUSIONS
  The study provides further evidence that the reported panel of diagnostic biomarkers can reliably achieve the noninvasive detection of bladder cancer with higher sensitivity than currently available urine based assays.
authors.affiliation: Nonagen Bioscience Corp., Orlando, Florida. Electronic address: deacdoc@aol.com.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
authors.forename: Shanti
authors.initials: S
authors.lastname: Ross
authors.forename: Myron
authors.initials: M
authors.lastname: Chang
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Dai
authors.forename: Lourdes
authors.initials: L
authors.lastname: Mengual
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Jeongsoon
authors.initials: J
authors.lastname: Kim
authors.forename: Virginia
authors.initials: V
authors.lastname: Urquidi
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcaraz
authors.forename: Steve
authors.initials: S
authors.lastname: Goodison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000652:urine; D016482:Urinalysis / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009363:Neoplasm Proteins
keywords: ANG; APOE; BCa; BIC; Bayesian information criterion; CA9; ELISA; IL-8; LUTS; MIBC; MMP; PAI-1; VEGF; VUC; angiogenin; apolipoprotein E; biological markers; bladder cancer; carbonic anhydrase 9; diagnosis; enzyme-linked immunosorbent assay; interleukin-8; lower urinary tract symptoms; matrix metalloproteinase; molecular biology; muscle invasive BCa; plasminogen activator inhibitor 1; urinary bladder neoplasms; urine; vascular endothelial growth factor; voided urine cytology