Highly sensitive and specific novel biomarkers for the diagnosis of transitional bladder carcinoma

// Prashant Kumar 1,* , Sayantani Nandi 1,* , Tuan Zea Tan 2,* , Siok Ghee Ler 3 , Kee Seng Chia 4 , Wei-Yen Lim 5 , Zentia Butow 6 , Dimitrios Vordos 6 , Alexandre De laTaille 6 , Muthafar Al-Haddawi 1 , Manfred Raida 7 , Burkhard Beyer 8 , Estelle Ricci 9 , Marc Colombel 9 , Tsung Wen Chong 10 , Edmund Chiong 11 , Ross Soo 12 , Mi Kyoung Park 13 , Hong Koo Ha 14,** , Jayantha Gunaratne 3,4,** and Jean Paul Thiery 1,2,7,** 1 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 2 Cancer Science Institute, National University of Singapore, Singapore 3 Quantitative Proteomics Group, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 4 Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 5 Saw Swee Hock School of Public Health, National University of Singapore, Singapore 6 CHU Hopital Henri Mondor, Department of Urology, Creteil, France 7 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 8 Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 9 Service d’Urologie et Chirurgie de la Transplantation, Hopital Edouard Herriot, Lyon, France 10 Department of Urology, Singapore General Hospital, Singapore 11 Department of Urology, University Surgical Cluster, National University Health System (NUHS), Singapore 12 Haematology-Oncology Research Group, Department of Haematology-Oncology, National University Cancer Institute (NCIS), National University Hospital, Singapore 13 Institute of Microelectronics (IME), A*STAR, Singapore 14 Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea * These authors are co-first authors ** These authors are co-senior authors Correspondence to: Jean Paul Thiery, email: // Keywords : transitional bladder carcinoma, urine biomarkers, receiving operating characteristics, combination model Received : December 08, 2014 Accepted : March 19, 2015 Published : April 15, 2015 Abstract Transitional bladder carcinoma (BCa) is prevalent in developed countries, particularly among men. Given that these tumors frequently recur or progress, the early detection and subsequent monitoring of BCa at different stages is critical. Current BCa diagnostic biomarkers are not sufficiently sensitive for substituting or complementing invasive cystoscopy. Here, we sought to identify a robust set of urine biomarkers for BCa detection. Using a high-resolution, mass spectrometry-based, quantitative proteomics approach, we measured, compared and validated protein variations in 451 voided urine samples from healthy subjects, non-bladder cancer patients and patients with non-invasive and invasive BCa. We identified five robust biomarkers: Coronin-1A, Apolipoprotein A4, Semenogelin-2, Gamma synuclein and DJ-1/PARK7. In diagnosing Ta/T1 BCa, these biomarkers achieved an AUC of 0.92 and 0.98, respectively, using ELISA and western blot data (sensitivity, 79.2% and 93.9%; specificity, 100% and 96.7%, respectively). In diagnosing T2/T3 BCa, an AUC of 0.94 and 1.0 was attained (sensitivity, 86.4% and 100%; specificity, 100%) using the same methods. Thus, our multiplex biomarker panel offers unprecedented accuracy for the diagnosis of BCa patients and provides the prospect for a non-invasive way to detect bladder cancer.