Prashant Kumar1,*, Sayantani Nandi1,*, Tuan Zea Tan2,*, Siok Ghee Ler3, Kee Seng Chia4, Wei-Yen Lim5, Zentia Bütow6, Dimitrios Vordos6, Alexandre De laTaille6, Muthafar Al-Haddawi1, Manfred Raida7, Burkhard Beyer8, Estelle Ricci9, Marc Colombel9, Tsung Wen Chong10, Edmund Chiong11, Ross Soo12, Mi Kyoung Park13, Hong Koo Ha14,**, Jayantha Gunaratne3,4,** and Jean Paul Thiery1,2,7,**
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 54 av du Marechal de Lattre de Tassigny Créteil – 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 Hôpital Edouard Herriot-5, place d’Arsonval, Lyon
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
* These authors are co first authors
** These authors are co-senior authors
Correspondence to: Jean Paul Thiery, email: firstname.lastname@example.org
Published online in Oncotarget on 15 April 2015.
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.
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Figure Legend: (A) Workflow for identification of bladder cancer urine biomarkers. qMS: quantitative Mass Spectrometry; GO: Gene Ontology; WB: Western blot (B) Receiver operating characteristic (ROC) curves designed to evaluate the accuracy of the multiplex biomarker model for the diagnosis of bladder carcinoma (BCa). This model assesses the efficacy of the biomarkers to distinguish both non-muscle invasive (NMI; Ta/T1) and muscle invasive (MI; T2/T3) BCa from healthy subjects based on data obtained from ELISA analysis (upper panel) and western blot analysis (lower panel) of voided urine samples.
For more information on Jean Paul THIERY laboratory, please click here and Jayantha GUNARATNE's laboratory, please click here.