Early diagnosis of bladder cancer through the detection of urinary tyrosine-phosphorylated proteins

• Published in: British journal of cancer Vol. 113; no. 3; pp. 469 - 475
• Main Authors: Khadjavi, A, Mannu, F, Destefanis, P, Sacerdote, C, Battaglia, A, Allasia, M, Fontana, D, Frea, B, Polidoro, S, Fiorito, G, Matullo, G, Pantaleo, A, Notarpietro, A, Prato, M, Castagno, F, Vineis, P, Gontero, P, Giribaldi, G, Turrini, F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.07.2015; Nature Publishing Group
• Subjects: 692/699/67/1857; 692/699/67/2322; 692/699/67/589/1336; 692/700/139/1420/1919; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - urine; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Cohort Studies; Drug Resistance; Early Detection of Cancer - methods; Epidemiology; Female; Humans; Male; Middle Aged; Molecular Diagnostics; Molecular Medicine; Neoplasm Staging; Oncology; Phosphoproteins - metabolism; Phosphoproteins - urine; Pilot Projects; Protein-Tyrosine Kinases - metabolism; Tyrosine - metabolism; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - urine; urinary tumour markers; urinary tyrosine-phosphorylated proteins; diagnostic assay; bladder cancer
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2015.232

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.