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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Mar 29 [Epub ahead of print]
Maria Frantzi, Kim E Van Kessel, Ellen C Zwarthoff, Mirari Marquez, Marta Rava, Nuria Malats, Axel S Merseburger, Ioannis Katafigiotis, Konstantinos Stravodimos, William Mullen, Jerome Zoidakis, Manousos Makridakis, Martin Pejchinovski, Elena Critselis, Ralf Lichtinghagen, Korbinian Brand, Mohammed Dakna, Maria G Roubelakis, Dan Theodorescu, Antonia Vlahou, H Mischak, Nicholas P Anagnou
Biomarkers Department, Mosaiques Diagnostics GmbH Department of Pathology, Erasmus Medical Center., Pathology, Erasmus MC., Genetic and Molecular Epidemiology, Spanish National Cancer Research Centre (CNIO)., Genetic and Molecular Epidemiology, Spanish National Cancer Research Centre (CNIO)., Genetic and Molecular Epidemiology, Spanish National Cancer Research Centre (CNIO)., Urology; campus Lubeck, University Hospital Schleswig-Holstein Ratzeburger., Department of Urology, Laikon Hospital, Medical School of Athens., Urology, Laikon Hospital, Medical School of Athens., Institute of Cardiovascular and Medical Sciences, University of Glasgow., Proteomics, Biomedical Research Foundation, Academy of Athens., Biotechnology Laboratory, Biomedical Research Foundation of the Academy of Athens (BRFAA)., Department of Biomarker Research, Mosaiques diagnostics GmbH., Biotechnology Division, Biomedical Research Foundation, Academy of Athens (BRFAA)., Institute of Clinical Chemistry, Medical School Hannover., Institute of Clinical Chemistry, Hannover Medical School., Research, mosaiques-diagnostics GmbH., Cell and Gene Therapy Laboratory, Biomedical Research Foundation , Academy of Athens (BRFAA)., Surgery and Pathology, University of Colorado Comprehensive Cancer Center., Biotechnology, Biomedical Research Foundation, Academy of Athens., Research, Mosaiques Diagnostics and Therapeutics AG., Laboratory of Biology, University of Athens School of Medicine.