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

TL;DR

SH3YL1 and NOX4 are linked to muscle-invasive bladder cancer progression and could help predict patient outcomes and treatment risks.

Contribution

Identifies SH3YL1 and NOX4 as novel biomarkers for muscle-invasive bladder cancer progression and prognosis.

Findings

SH3YL1 levels are elevated in bladder cancer patients, not due to cisplatin-induced kidney injury.

SH3YL1 and NOX4 are significantly overexpressed in muscle-invasive bladder cancer compared to non-muscle-invasive cases.

Low SH3YL1 expression correlates with poor survival in muscle-invasive bladder cancer patients.

Abstract

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 SH3YL1 as a potential biomarker for bladder cancer progression and AKI. Plasma and urine SH3YL1 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 SH3YL1’s interactions with NADPH oxidase pathways, particularly NOX family genes, and highlighted its roles in cell adhesion, migration, and cytoskeletal organization—processes critical for tumor invasiveness. Notably, SH3YL1 and NOX4 expression were significantly higher in MIBC than in non-muscle-invasive bladder cancer (NMIBC), with a strong correlation between SH3YL1 and NOX4 (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 SH3YL1 expression is significantly associated with poor overall and disease-specific survival in MIBC patients, reinforcing its role as a prognostic biomarker. In conclusion, SH3YL1 is a promising biomarker for identifying the invasive characteristics of MIBC and predicting patient outcomes. These findings underscore the importance of SH3YL1–NOX4 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.

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