Identification of a Highly Sensitive Combination of Urinary Protein Biomarkers for the Detection of High-Grade Bladder Cancer

Purpose: Bladder cancer is the ninth most common malignancy worldwide and poses a significant diagnostic challenge due to high recurrence rates and dependence on invasive procedures such as cystoscopy. Urine cytology, a commonly used noninvasive test, suffers from low sensitivity, particularly for high-grade tumors. This study aimed to identify a panel of urinary protein biomarkers capable of reliably detecting high-grade bladder cancer through a noninvasive approach. Methods: Urinary samples from patients with confirmed bladder cancer and from control individuals were analyzed using mass spectrometry-based proteomics. Differential protein expression was assessed to identify potential diagnostic markers. Candidate proteins were selected based on consistent overexpression in cancer samples and validated using statistical modeling. Results: A combination of 4 proteins—Complement Factor H, Fibrinogen β, Alpha-2-macroglobulin, and Pancreatic Alpha-amylase—showed strong diagnostic potential. This panel achieved 100% sensitivity for high-grade tumor detection, with a false-positive rate below 20%, depending on patient history. The biomarker panel outperformed traditional cytology, particularly for early-stage tumors. Limitations include sample size and the need for external validation in larger, multicenter cohorts. Conclusions: The identified urinary protein panel offers a promising noninvasive alternative for the detection of high-grade bladder cancer. This approach could significantly improve early diagnosis, reduce reliance on invasive procedures, and enhance patient follow-up. Future validation studies may support its integration into clinical practice as a cost-effective diagnostic tool.