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Highly sensitive and specific novel biomarkers for the diagnosis of transitional bladder carcinoma
Authors:Prashant Kumar  Sayantani Nandi  Tuan Zea Tan  Siok Ghee Ler  Kee Seng Chia  Wei-Yen Lim  Zentia Bütow  Dimitrios Vordos  Alexandre De laTaille  Muthafar Al-Haddawi  Manfred Raida  Burkhard Beyer  Estelle Ricci  Marc Colombel  Tsung Wen Chong  Edmund Chiong  Ross Soo  Mi Kyoung Park  Hong Koo Ha  Jayantha Gunaratne  Jean Paul Thiery
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.
Keywords:transitional bladder carcinoma   urine biomarkers   receiving operating characteristics   combination model
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