Highly sensitive and specific novel biomarkers for the diagnosis of transitional bladder carcinoma.
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.
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore.
Prashant
P
Kumar
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore.
Sayantani
S
Nandi
Cancer Science Institute, National University of Singapore, Singapore.
Tuan Zea
TZ
Tan
Quantitative Proteomics Group, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
Siok Ghee
SG
Ler
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Kee Seng
KS
Chia
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
Wei-Yen
WY
Lim
CHU Hopital Henri Mondor, Department of Urology, Créteil, France.
Zentia
Z
Bütow
CHU Hopital Henri Mondor, Department of Urology, Créteil, France.
Dimitrios
D
Vordos
CHU Hopital Henri Mondor, Department of Urology, Créteil, France.
Alexandre
A
De la Taille
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore.
Muthafar
M
Al-Haddawi
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Manfred
M
Raida
Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Burkhard
B
Beyer
Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot, Lyon, France.
Estelle
E
Ricci
Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot, Lyon, France.
Marc
M
Colombel
Department of Urology, Singapore General Hospital, Singapore.
Tsung Wen
TW
Chong
Department of Urology, University Surgical Cluster, National University Health System (NUHS), Singapore.
Edmund
E
Chiong
Haematology-Oncology Research Group, Department of Haematology-Oncology, National University Cancer Institute (NCIS), National University Hospital, Singapore.
Ross
R
Soo
Institute of Microelectronics (IME), A*STAR, Singapore.
Mi Kyoung
MK
Park
Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.
Hong Koo
HK
Ha
Quantitative Proteomics Group, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.|Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Jayantha
J
Gunaratne
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore.|Cancer Science Institute, National University of Singapore, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Jean Paul
JP
Thiery
D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D016022:Case-Control Studies; D015331:Cohort Studies; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000473:pathology / Q000652:urine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine
D014408:Biomarkers, Tumor
combination model; receiving operating characteristics; transitional bladder carcinoma; urine biomarkers