Integrated Proteogenomic Approach for Discovering Potential Biomarkers in Urothelial Carcinoma of the Bladder

Background/Objectives: Urothelial carcinoma of the bladder (UCC) is a leading cause of cancer-related death globally. Given that urine is in direct contact with the tumor, it represents a highly valuable source for non-invasive molecular analysis. Methods: This study utilized liquid biopsies from 41 UCC patients and 27 non-cancerous hematuria controls to identify novel diagnostic and prognostic biomarkers via proteomic and transcriptomic analysis. Results: Urine proved to be a reliable source, yielding a mean tumor cell fraction of 0.605 (95% CI: 0.505-0.705). We identified 11 genes with concurrent alteration at both the urinary protein and mRNA levels. Notably, four upregulated markers, CYTB, C1QC, SBP1, and ANXA4, demonstrated strong diagnostic potential, with AUC values greater than 0.70. CYTB and ANXA4 were detectable even in early-stage UCC (stages Cis, I, and II). Furthermore, we identified two proteins, CATC and SPB10, that were markedly upregulated in recurrent UCC and correlated with poor overall survival, positioning them as potential prognostic markers for recurrence risk. Conclusions: This study confirms the utility of urine as a reliable medium for detecting UCC tumor cells, offering promising markers for both early-stage diagnosis and predicting NMIBC recurrence.