The grade of systemic inflammation, immune inhibition, and gut dysbiosis as prognostic factors for bladder cancer recurrence: a metabolomics approach

BACKGROUND: The risk of recurrence for non-muscle invasive bladder cancer (NMIBC) is high, and the current methods of predicting it rely on clinical and histopathological markers. Personalized risk assessment can be improved by including new prognostic biomarkers. Our research explores the potential of urinary metabolomics to predict cancer recurrence in NMIBC patients within three years.METHODS: Fifty NMIBC patients were included in the study. Urine samples were collected at diagnosis and before TUR-BT. After three years, patients were classified as relapsed or non-relapsed. An NMR-based metabolomics approach was used to measure the concentration of 44 metabolites in the urine of these patients at the time of their diagnosis. This method provides a comprehensive view of many urinary compounds potentially valuable for discriminating relapsing from non-relapsing patients. The measured metabolic profiles were analyzed through multivariate analysis, probability ROC curves, and Mann-Whitney tests.RESULTS: Seven metabolites were involved in NMIBC recurrence prediction. We interpret their alteration as the consequence of three main events: gut dysbiosis, systemic inflammation, and immune inhibition. Since these compounds have already been proposed for BC diagnosis, what distinguishes their role as prognostic or diagnostic is the grade of their alteration. Limitations: small sample size; further research to confirm urinary compounds' correlation with physiological processes.CONCLUSIONS: This study exploits urinary metabolic profiles to predict NMIBC recurrence. Specific metabolites are found to be significantly related to cancer relapse. The study highlights the grade of inflammation, immune suppression, and gut dysbiosis in predicting cancer recurrence.