Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. The top hits were subjected to systems biology analyses. MethodsĪn aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA.
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