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

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 Oncotarget 13540 www.impactjournals.com/oncotarget

Virus Bioresistor (VBR) for Detection of Bladder Cancer Marker DJ-1 in Urine at 10 pM in One Minute

“…With this modification, a limit-of-detection of (LOD DJ1 ) of 10 pM is achieved in urine (synthetic and human), coupled with a dynamic range of more than four orders of magnitude from 10 pM to 300 nM. This performance is clinically relevant because it allows for the detection of elevated DJ-1 in the urine of patients who have bladder cancer (≈ 100 pM). ,,, Importantly, the modifications to the VBR do not compromise either the speed or the simplicity of its operation. As before, the VBR operates in a dip-and-read modality and produces a stable, quantitative signal within 1.0 min.…”

“…This performance is clinically relevant because it allows for the detection of elevated DJ-1 in the urine of patients who have bladder cancer (≈ 100 pM). 2,3,5,6 Importantly, the modifications to the VBR do not compromise either the speed or the simplicity of its operation. As before, 4 the VBR operates in a dip-and-read modality and produces a stable, quantitative signal within 1.0 min.…”