title: Early diagnosis of bladder cancer through the detection of urinary tyrosine-phosphorylated proteins.
abstract: BACKGROUND
  A noninvasive, highly sensitive and specific urine test is needed for bladder cancer (BC) diagnosis and surveillance in addition to the invasive cystoscopy. We previously described the diagnostic effectiveness of urinary tyrosine-phosphorylated proteins (UPY) and a new assay (UPY-A) for their measurement in a pilot study. The aim of this work was to evaluate the performances of the UPY-A using an independent cohort of 262 subjects.
  
  
  METHODS
  Urinary tyrosine-phosphorylated proteins were measured by UPY-A test. The area under ROC curve, cutoff, sensitivity, specificity and predictive values of UPY-A were determined. The association of UPY levels with tumour staging, grading, recurrence and progression risk was analysed by Kruskal-Wallis and Wilcoxon's test. To test the probability to be a case if positive at the UPY-A, a logistic test adjusted for possible confounding factor was used.
  
  
  RESULTS
  Results showed a significant difference of UPY levels between patients with BC vs healthy controls. For the best cutoff value, 261.26 Standard Units (SU), the sensitivity of the assay was 80.43% and the specificity was 78.82%. A statistically significant difference was found in the levels of UPY at different BC stages and grades between Ta and T1 and with different risk of recurrence and progression. A statistically significant increased risk for BC at UPY-A ⩾261.26 SU was observed.
  
  
  CONCLUSIONS
  The present study supplies important information on the diagnostic characteristics of UPY-A revealing remarkable performances for early stages and allowing its potential use for different applications encompassing the screening of high-risk subjects, primary diagnosis and posttreatment surveillance.
authors.affiliation: Department of Neurosciences, University of Turin, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Khadjavi
authors.affiliation: Nurex s.r.l., Sassari, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mannu
authors.affiliation: Urology Clinic, Città della Salute e della Scienza di Torino, Hospital San Giovanni Battista, Department of Surgical Sciences, University of Turin, Torino, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Destefanis
authors.affiliation: Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin and Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Sacerdote
authors.affiliation: Urology Clinic, Città della Salute e della Scienza di Torino, Hospital San Giovanni Battista, Department of Surgical Sciences, University of Turin, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Battaglia
authors.affiliation: Urology Clinic, Città della Salute e della Scienza di Torino, Hospital San Giovanni Battista, Department of Surgical Sciences, University of Turin, Torino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Allasia
authors.affiliation: Urology Clinic, Città della Salute e della Scienza di Torino, Hospital San Giovanni Battista, Department of Surgical Sciences, University of Turin, Torino, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Fontana
authors.affiliation: Urology Clinic, Città della Salute e della Scienza di Torino, Hospital San Giovanni Battista, Department of Surgical Sciences, University of Turin, Torino, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Frea
authors.affiliation: HuGeF Human Genetics Foundation and Department of Medical Sciences, University of Turin, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Polidoro
authors.affiliation: HuGeF Human Genetics Foundation and Department of Medical Sciences, University of Turin, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Fiorito
authors.affiliation: HuGeF Human Genetics Foundation and Department of Medical Sciences, University of Turin, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Matullo
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pantaleo
authors.affiliation: Department of Oncology, University of Turin Medical School, University of Turin, via Santena 5 BIS, Torino 10126, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Notarpietro
authors.affiliation: Department of Neurosciences, University of Turin, Torino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Prato
authors.affiliation: Blood Center, AO Città della Salute e della Scienza di Torino, Hospital San Giovanni Battista, Torino, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Castagno
authors.affiliation: MRC-PHE Center for Environment and Health, School of Public Health, Imperial College, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Vineis
authors.affiliation: Urology Clinic, Città della Salute e della Scienza di Torino, Hospital San Giovanni Battista, Department of Surgical Sciences, University of Turin, Torino, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Gontero
authors.affiliation: Department of Oncology, University of Turin Medical School, University of Turin, via Santena 5 BIS, Torino 10126, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Giribaldi
authors.affiliation: Department of Oncology, University of Turin Medical School, University of Turin, via Santena 5 BIS, Torino 10126, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Turrini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D016022:Case-Control Studies; D015331:Cohort Studies; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000378:metabolism / Q000652:urine*; D010865:Pilot Projects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases