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

Li Mei Chen, Myron Chang, Yunfeng Dai, Karl X. Chai, Lars Dyrskjøt, Marta Sanchez-Carbayo, Tibor Szarvas, Ellen C. Zwarthoff, Vinata B Lokeshwar, Carmen Jeronimo, Alexander S. Parker, Shanti Ross, Michael Borre, Torben F. Ørntoft, Tobias Jaeger, Willemien Beukers, Luis E. Lopez, Rui Henrique, Paul R. Young, Virginia Urquidi & 2 others Steve Goodison, Charles J. Rosser

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1804-1812
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number9
DOIs
StatePublished - Sep 1 2014

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Urinary Bladder Neoplasms
Biomarkers
Proteins
Muscle Neoplasms
Sensitivity and Specificity
Validation Studies
Apolipoproteins E
Interleukin-8
Enzyme-Linked Immunosorbent Assay
Quality of Life
Urine
Confidence Intervals
Survival

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

External validation of a multiplex urinary protein panel for the detection of bladder cancer in a multicenter cohort. / Chen, Li Mei; Chang, Myron; Dai, Yunfeng; Chai, Karl X.; Dyrskjøt, Lars; Sanchez-Carbayo, Marta; Szarvas, Tibor; Zwarthoff, Ellen C.; Lokeshwar, Vinata B; Jeronimo, Carmen; Parker, Alexander S.; Ross, Shanti; Borre, Michael; Ørntoft, Torben F.; Jaeger, Tobias; Beukers, Willemien; Lopez, Luis E.; Henrique, Rui; Young, Paul R.; Urquidi, Virginia; Goodison, Steve; Rosser, Charles J.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 23, No. 9, 01.09.2014, p. 1804-1812.

Research output: Contribution to journalArticle

Chen, LM, Chang, M, Dai, Y, Chai, KX, Dyrskjøt, L, Sanchez-Carbayo, M, Szarvas, T, Zwarthoff, EC, Lokeshwar, VB, Jeronimo, C, Parker, AS, Ross, S, Borre, M, Ørntoft, TF, Jaeger, T, Beukers, W, Lopez, LE, Henrique, R, Young, PR, Urquidi, V, Goodison, S & Rosser, CJ 2014, 'External validation of a multiplex urinary protein panel for the detection of bladder cancer in a multicenter cohort', Cancer Epidemiology Biomarkers and Prevention, vol. 23, no. 9, pp. 1804-1812. https://doi.org/10.1158/1055-9965.EPI-14-0029
Chen, Li Mei ; Chang, Myron ; Dai, Yunfeng ; Chai, Karl X. ; Dyrskjøt, Lars ; Sanchez-Carbayo, Marta ; Szarvas, Tibor ; Zwarthoff, Ellen C. ; Lokeshwar, Vinata B ; Jeronimo, Carmen ; Parker, Alexander S. ; Ross, Shanti ; Borre, Michael ; Ørntoft, Torben F. ; Jaeger, Tobias ; Beukers, Willemien ; Lopez, Luis E. ; Henrique, Rui ; Young, Paul R. ; Urquidi, Virginia ; Goodison, Steve ; Rosser, Charles J. / External validation of a multiplex urinary protein panel for the detection of bladder cancer in a multicenter cohort. In: Cancer Epidemiology Biomarkers and Prevention. 2014 ; Vol. 23, No. 9. pp. 1804-1812.
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T1 - External validation of a multiplex urinary protein panel for the detection of bladder cancer in a multicenter cohort

AU - Chen, Li Mei

AU - Chang, Myron

AU - Dai, Yunfeng

AU - Chai, Karl X.

AU - Dyrskjøt, Lars

AU - Sanchez-Carbayo, Marta

AU - Szarvas, Tibor

AU - Zwarthoff, Ellen C.

AU - Lokeshwar, Vinata B

AU - Jeronimo, Carmen

AU - Parker, Alexander S.

AU - Ross, Shanti

AU - Borre, Michael

AU - Ørntoft, Torben F.

AU - Jaeger, Tobias

AU - Beukers, Willemien

AU - Lopez, Luis E.

AU - Henrique, Rui

AU - Young, Paul R.

AU - Urquidi, Virginia

AU - Goodison, Steve

AU - Rosser, Charles J.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.

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