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Cancer Epidemiol Biomarkers Prev. 2014 Sep;23(9):1804-12. doi: 10.1158/1055-9965.EPI-14-0029. Epub 2014 Jun 11.

External validation of a multiplex urinary protein panel for the detection of bladder cancer in a multicenter cohort.

Author information

1
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida.
2
Department of Biostatistics, The University of Florida, Gainesville, Florida.
3
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
4
Bladder Cancer Group, Proteomics Unit, Bizkaia, Spain.
5
Department of Urology, University Hospital Duisburg-Essen, Essen, Germany.
6
Department of Pathology, Erasmus MC, Rotterdam, the Netherlands.
7
Department of Urology, University of Miami Miller School of Medicine, Miami, Florida. Department of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida.
8
Cancer Epigenetics Group, Research Center Portuguese Oncology Institute, Porto, Portugal. Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal.
9
Department of Urology, Mayo Clinic Florida, Jacksonville, Florida.
10
Cancer Research Institute, MD Anderson Cancer Center, Orlando, Florida.
11
Cancer Research Institute, MD Anderson Cancer Center, Orlando, Florida. Nonagen Bioscience Corp., Jacksonville, Florida.
12
Cancer Research Institute, MD Anderson Cancer Center, Orlando, Florida. Nonagen Bioscience Corp., Jacksonville, Florida. Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida.
13
Cancer Research Institute, MD Anderson Cancer Center, Orlando, Florida. Nonagen Bioscience Corp., Jacksonville, Florida. University of Hawaii, Honolulu, Hawaii. crosser@cc.hawaii.edu.

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.

PMID:
24920641
PMCID:
PMC4154967
DOI:
10.1158/1055-9965.EPI-14-0029
[Indexed for MEDLINE]
Free PMC Article

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