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

Urothelial carcinoma of the bladder (UCC) is the ninth most common causes of cancer death worldwide. Urine, which directly contact with UCC tumor, offers a convenient way to identify tumor cells and serves as a novel diagnostic tool. Our study aimed to elucidate the molecular mechanisms and discover potential biomarkers by analyzing liquid biopsies from UCC patients. We performed proteomic and transcriptomic analyses on urine samples from 41 UCC and 27 patients with non-cancerous hematuria. We found that urine was a dependable source for tumor cell detection, with a mean tumor cell fraction of 0.605 (95% CI : 0.505 - 0.705). Our proteogenomic analysis revealed 11 genes that were altered at both the urinary protein and mRNA levels. Notably, three of these genes, namely CYTB, SBP1, and ANXA4, showed upregulation with AUC values exceeding 0.750. CYTB and ANXA4 were detectable even in the early stages of UCC (Stage Cis, I, and II). Furthermore, we identified 2 proteins, including CATC, and SPB10, that were markedly upregulated in recurrent UCC and correlated with poor overall survival. This finding highlights their potential as strong candidates for diagnostic markers in the early stages of UCC, and as prognostic marker for recurrence prediction.