A Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer

• Published in: PloS one Vol. 7; no. 10; p. e47469
• Main Authors: Goodison, Steve, Chang, Myron, Dai, Yunfeng, Urquidi, Virginia, Rosser, Charles J.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.10.2012; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - urine; Assaying; Biological markers; Biomarkers; Biomarkers, Tumor - urine; Bladder; Bladder cancer; Cancer; Carcinoma - diagnosis; Carcinoma - pathology; Carcinoma - urine; Case-Control Studies; CCL18 protein; CD44 antigen; Cell growth; Cellular biology; Cytokines; Cytology; Diagnosis; Diagnostic systems; Enzyme-Linked Immunosorbent Assay; Enzymes; Female; Gelatinase B; Health care; Humans; Interleukin 8; Interleukin-8 - urine; Laboratories; Male; Medical diagnosis; Medical research; Medicine; Middle Aged; Multivariate Analysis; Neoplasm Grading; Neoplasm Staging; Patients; Polyamide-imides; Proteins; Proteomics; R&D; Research & development; ROC Curve; Sensitivity; Statistical tests; Stromelysin 2; Tumors; Urinary bladder; Urinary Bladder - metabolism; Urinary Bladder - pathology; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - urine; Urine; Urology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - urine; Florida; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0047469

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.