Development and validation of urine-based peptide biomarker panels for detecting bladder cancer in a multi-center study

Frantzi, M. et al. (2016) Development and validation of urine-based peptide biomarker panels for detecting bladder cancer in a multi-center study. Clinical Cancer Research, 22(16), pp. 4077-4086. (doi: 10.1158/1078-0432.CCR-15-2715) (PMID:27026199)

Abstract

Purpose: Urothelial bladder cancer (UBC) presents high recurrence rates, mandating continuous monitoring via invasive cystoscopy. The development of non-invasive tests for disease diagnosis and surveillance remains an unmet clinical need. In this study, validation of two urine-based biomarker panels for detecting primary and recurrent UBC was conducted. Experimental Design: Two studies (total n=1357) were performed for detecting primary (n=721) and relapsed UBC (n=636). Cystoscopy was applied for detecting UBC, while patients negative for recurrence had follow-up for at least one year to exclude presence of an undetected tumor at the time of sampling. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was employed for the identification of urinary peptide biomarkers. The candidate urine-based peptide biomarker panels were derived from nested cross-sectional studies in primary (n=451) and recurrent (n=425) UBC. Results: Two biomarker panels were developed based on 116 and 106 peptide biomarkers using support vector machine algorithms. Validation of the urine-based biomarker panels in independent validation sets, resulted in AUC values of 0.87 and 0.75 for detecting primary (n=270) and recurrent UBC (n=211), respectively. At the optimal threshold, the classifier for detecting primary UBC exhibited 91% sensitivity and 68% specificity, while the classifier for recurrence demonstrated 87% sensitivity and 51% specificity. Particularly for patients undergoing surveillance, improved performance was achieved when combining the urine-based panel with cytology (AUC of 0.87). Conclusions: The developed urine-based peptide biomarker panel for detecting primary UBC exhibits good performance. Combination of the urine-based panel and cytology resulted in improved performance for detecting disease recurrence.

• Item Type: Articles
• Additional Information: This work was supported in part by the BCMolMed grant PITN-GA-2012-317450 BCMolMed, TransBioBC grant (601933) from the FP7-Health project, Uromol FP7/2007-2012, Grant Agreement 201663 and DECanBio EU FP7-HEALTH-F2-2008-201333-DECanBio, projects funded by the European Commission
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Frantzi, Ms Maria and Mullen, Dr Bill and Mischak, Professor Harald
• Authors: Frantzi, M., Van Kessel, K. E., Zwarthoff, E. C., Marquez, M., Rava, M., Malats, N., Merseburger, A. S., Katafigiotis, I., Stravodimos, K., Mullen, W., Zoidakis, J., Makridakis, M., Pejchinovski, M., Critselis, E., Lichtinghagen, R., Brand, K., Dakna, M., Roubelakis, M. G., Theodorescu, D., Vlahou, A., Mischak, H., and Anagnou, N. P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Clinical Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 1078-0432
• ISSN (Online): 1557-3265
• Published Online: 29 March 2016
• Copyright Holders: Copyright © 2016 American Association for Cancer Research
• First Published: First published in Clinical Cancer Research 22(16): 4077-4086
• Publisher Policy: Reproduced in accordance with the publisher copyright policy