title: A multiplex urinary immunoassay for bladder cancer detection: analysis of a Japanese cohort.
abstract: Bladder cancer (BCa) is among the most commonly diagnosed malignancies worldwide, and due the high rate of post-operative disease recurrence, it is one of the most prevalent in many countries. The development of non-invasive molecular assays that can accurately detect and monitor BCa would be a major advance, benefiting both patients and healthcare systems. We have previously identified a urinary protein biomarker panel that is being developed for application in at-risk patient cohorts. Here, we investigated the potential utility of the multiplex assay in a Japanese cohort.
  
  
  
  The Japanese study cohort collected from urology clinics at two institutions was comprised of a total of 288 subjects. The protein biomarker panel (IL8, MMP9, MMP10, ANG, APOE, SDC1, A1AT, PAI1, CA9, VEGFA) was monitored in voided urine samples collected prior to cystoscopy using a custom multiplex ELISA assay. The diagnostic performance of the biomarker panel was assessed using receiver operator curves, predictive modeling and descriptive statistics.
  
  
  
  Urinary biomarker concentrations were significantly elevated in cases versus controls, and in cases with high-grade and muscle-invasive tumors. The AUC for the 10-biomarker assay was 0.892 (95 % confidence interval 0.850-0.934), with an overall diagnostic sensitivity specificity of 0.85 and 0.81, respectively. A predictive model trained on the larger institutional cohort correctly identified 99 % of the cases from the second institution.
  
  
  
  Urinary levels of a 10-biomarker panel enabled discrimination of patients with BCa. The multiplex urinary diagnostic assay has the potential to be developed for the non-invasive detection of BCa in at-risk Japanese patients.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.|Mayo Clinic Cancer Center, Rochester, MN, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Goodison
authors.affiliation: Department of Urology, Kyoto University, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.affiliation: Department of Urology, Kyoto University, Kyoto, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Department of Urology, Kyoto University, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Urology, Nara Medical University, Nara, Japan.
authors.forename: Makito
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Department of Urology, Nara Medical University, Nara, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Ohnishi
authors.affiliation: Department of Urology, Nara Medical University, Nara, Japan.
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Biostatistics, The University of Florida, Gainesville, FL, USA.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Clinical and Translational Research Program, University of Hawaii Cancer Center, 701 Ilalo St, Rm 327, Honolulu, HI, 96813, USA.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Clinical and Translational Research Program, University of Hawaii Cancer Center, 701 Ilalo St, Rm 327, Honolulu, HI, 96813, USA.
authors.forename: Kazue
authors.initials: K
authors.lastname: Tsukikawa
authors.affiliation: Clinical and Translational Research Program, University of Hawaii Cancer Center, 701 Ilalo St, Rm 327, Honolulu, HI, 96813, USA.
authors.forename: Hideki
authors.initials: H
authors.lastname: Furuya
authors.affiliation: Clinical and Translational Research Program, University of Hawaii Cancer Center, 701 Ilalo St, Rm 327, Honolulu, HI, 96813, USA. cjrosser@hawaii.edu.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D014408:Biomarkers, Tumor / Q000652:urine; D015331:Cohort Studies; D003710:Demography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarkers; Bladder cancer; Multiplex; Protein; Urine