External Validation of a Multiplex Urinary Protein Panel for the Detection of Bladder Cancer in a Multicenter Cohort

    Authors

    L. M. Chen; M. R. Chang; Y. F. Dai; K. X. Chai; L. Dyrskjot; M. Sanchez-Carbayo; T. Szarvas; E. C. Zwarthoff; V. Lokeshwar; C. Jeronimo; A. S. Parker; S. Ross; M. Borre; T. F. Orntoft; T. Jaeger; W. Beukers; L. E. Lopez; R. Henrique; P. R. Young; V. Urquidi; S. Goodison;C. J. Rosser

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    Abbreviated Journal Title

    Cancer Epidemiol. Biomarkers Prev.

    Keywords

    TRANSITIONAL-CELL CARCINOMA; NUCLEAR-MATRIX PROTEIN; BTA TRAK ASSAY; GENE-EXPRESSION; TUMOR MARKERS; CYTOLOGY; DIAGNOSIS; SURVEILLANCE; PROGRESSION; IDENTIFICATION; Oncology; Public, Environmental & Occupational Health

    Abstract

    Background: Because of the faltering sensitivity and/or specificity, urine-based assays currently have a limited role in the management of patients with bladder cancer. The aim of this study was to externally validate our previously reported protein biomarker panel from multiple sites in the United States and Europe. Methods: This multicenter external validation study included a total of 320 subjects (bladder cancer = 183). The 10 biomarkers (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SDC1, and SERPINE1) were measured using commercial ELISA assays in an external laboratory. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values. Results: Utilizing the combination of all 10 biomarkers, the area under the ROC for the diagnostic panel was noted to be 0.847 (95% confidence interval, 0.796-0.899), outperforming any single biomarker. The multiplex assay at optimal cutoff value achieved an overall sensitivity of 0.79, specificity of 0.79, positive prediction value of 0.73, and negative prediction value of 0.84 for bladder cancer classification. Sensitivity values of the diagnostic panel for high-grade bladder cancer, low-grade bladder cancer, muscle invasive bladder cancer, and non-muscle invasive bladder cancer were 0.81, 0.90, 0.95, and 0.77, respectively. Conclusions: Urinary levels of the biomarker panel enabled discrimination of patients with bladder cancer and controls, and the levels of biomarker subsets were associated with advancing tumor grade and stage. Impact: If proven to be reliable, urinary diagnostic biomarker assays can detect bladder cancer in a timely manner such that the patient can expect improvements in overall survival and quality of life. (C) 2014 AACR.

    Journal Title

    Cancer Epidemiology Biomarkers & Prevention

    Volume

    23

    Issue/Number

    9

    Publication Date

    1-1-2014

    Document Type

    Article

    Language

    English

    First Page

    1804

    Last Page

    1812

    WOS Identifier

    WOS:000345276100009

    ISSN

    1055-9965

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