Serum Biomarkers in Bladder Cancer: NMR Metabolomics for Identification and Monitoring during Platinum-Based Therapy

Objectives: To date, predictive and prognostic biomarkers for Bladder Cancer (BC) remain lacking. Existing literature underscores the potential of metabolomics as a valuable tool for biomarker identification. The primary objective of this study is to characterize the serum metabolic profile of BC patients undergoing platinum-based chemotherapy (Pt-CT) to identify potential biomarkers. Methods: In this pilot study, we investigated the metabolomic profiles of 14 BC patients undergoing Pt-CT in different settings. We compared their baseline profiles with those of healthy controls and tracked key metabolites throughout chemotherapy cycles. Metabolomics profiling was conducted using nuclear magnetic resonance (NMR) spectroscopy. All experiments were performed on a Bruker Avance™ 600 spectrometer. Results: Serum samples of BC patients had elevated levels of acetate, acetone, hypoxanthine, trimethylamine N-oxide (TMAO), glutamate, lactate, phenylalanine, and ornithine. Conversely, there were decreased levels of carnitine, choline, betaine, aspartate, threonine, 2-hydroxybutyrate, 2-aminobutyrate and histidine when compared with healthy controls. Throughout the CT course, hypoxanthine, glutamate, and aspartate levels increased, while acetone, acetate and TMAO levels decreased. Conclusions: The results of our study confirm perturbations in several metabolic pathways in the serum samples of BC patients, including glycolysis, fatty acid, purine, and amino acid metabolism. Additionally, TMAO may contribute to BC development by fostering a pro-inflammatory and oxidative stress state. Furthermore, monitoring these metabolites could serve as a valuable tool for predicting treatment response. To the best of our knowledge, no metabolomic studies have assessed BC patients undergoing CT with longitudinal monitoring to identify changes in the metabolic profile induced by treatment.