title: A multi-analyte assay for the non-invasive detection of bladder cancer.
abstract: Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.
authors.affiliation: Cancer Research Institute, M.D. Anderson Cancer Center Orlando, Orlando, Florida, United States of America.
authors.forename: Steve
authors.initials: S
authors.lastname: Goodison
authors.forename: Myron
authors.initials: M
authors.lastname: Chang
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Dai
authors.forename: Virginia
authors.initials: V
authors.lastname: Urquidi
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D002277:Carcinoma / Q000175:diagnosis / Q000473:pathology / Q000652:urine*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D012372:ROC Curve; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000652:urine*; D042461:Vascular Endothelial Growth Factor A / Q000652:urine*
chemical_list: D001057:Apolipoproteins E; D014408:Biomarkers, Tumor; D016209:Interleukin-8; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A