Diagnostic and Prognostic Potential of SH3YL1 and NOX4 in Muscle-Invasive Bladder Cancer

Bladder cancer, especially muscle-invasive bladder cancer (MIBC), poses significant treatment challenges due to its aggressive nature and poor prognosis, often necessitating cisplatin-based chemotherapy. While cisplatin effectively reduces tumor burden, its nephrotoxic effects, specifically cisplatin-induced acute kidney injury (AKI), limit its clinical use. This study investigates <i>SH3YL1</i> as a potential biomarker for bladder cancer progression and AKI. Plasma and urine <i>SH3YL1</i> levels were measured in bladder cancer patients undergoing cisplatin treatment, showing elevated baseline levels compared to controls, suggesting a link with bladder cancer pathology rather than cisplatin-induced AKI. Functional network and Gene Ontology (GO) enrichment analyses identified <i>SH3YL1</i>'s interactions with NADPH oxidase pathways, particularly <i>NOX</i> family genes, and highlighted its roles in cell adhesion, migration, and cytoskeletal organization-processes critical for tumor invasiveness. Notably, <i>SH3YL1</i> and <i>NOX4</i> expression were significantly higher in MIBC than in non-muscle-invasive bladder cancer (NMIBC), with a strong correlation between <i>SH3YL1</i> and <i>NOX4</i> (r = 0.62) in MIBC, suggesting a subtype-specific interaction. Kaplan-Meier survival analysis using The Cancer Genome Atlas bladder cancer (TCGA-BLCA) data further demonstrated that low <i>SH3YL1</i> expression is significantly associated with poor overall and disease-specific survival in MIBC patients, reinforcing its role as a prognostic biomarker. In conclusion, <i>SH3YL1</i> is a promising biomarker for identifying the invasive characteristics of MIBC and predicting patient outcomes. These findings underscore the importance of <i>SH3YL1-NOX4</i> pathways in MIBC and suggest the need for further research into targeted biomarkers for bladder cancer progression and cisplatin-induced AKI to improve patient outcomes in high-risk cases.