Proteomic Profiling of Plasma-Derived Biomarkers in Patients with Bladder Cancer: A Step towards Clinical Translation

Abstract

Background: Bladder cancer is a life-threatening disease and a major cause of cancer-associated complications. The main challenges confronted during the clinical management of bladder cancer are associated with recurrence and disease progression to the muscle-invasive phenotype. Improved early detection of the disease is of paramount importance to prevent disease progression and improve survival. Hence, novel clinically applicable biomarkers for early detection are warranted. Methods: In the current study, a comparative proteomic approach was undertaken using plasma samples to identify protein biomarkers associated with the muscle-invasive phenotype of bladder carcinoma. Isolated plasma proteins were depleted, DIGE-labeled, then subjected to conventional 2D electrophoresis followed by mass spectrometry for identification of differentially expressed proteins. Western blot was used for data validation. Results: Fourteen differentially expressed proteins with statistically significant changes in abundance between the cancer group and control group were identified. Three differentially expressed proteins were selected for validation, among which apolipoprotein A1 exhibited high specificity and sensitivity (AUC = 0.906). Ingenuity pathway analysis identified IFN-γ and TNF-α as the main signaling hub for the differentially regulated proteins. Conclusion: Our findings provide additional insight into understanding bladder cancer pathogenesis. Our data identified potential non-invasive plasma-derived biomarker proteins that merit additional investigation to validate its clinical usefulness to prevent bladder cancer progression.

Keywords

• bladder cancer
• biomarkers
• proteomics
• plasma
• 2D-DIGE
• mass spectrometry