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

Roberta Giorgione1,#, Daniela Grasso2,#, Elisabetta Gambale1, Federico Scolari3, Virginia Rossi1, Fabrizio Di Maida4, Marinella Micol Mela1, Barbara Marzocchi2, Laura Doni1, Adriano Pasqui1, Andrea Minervini4, Enrico Caliman1, Sergio Serni4,5,6, Andrea Bernini2, Serena Pillozzi3, Lorenzo Antonuzzo1,5,*
1 Oncology Unit, Careggi University Hospital, Florence, Italy
2 Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
3 Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
4 Unit of Urology and Andrology, Careggi University Hospital, Florence, Italy
5 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
6 Unit of Urology and Renal Transplantation, Careggi University Hospital, Florence, Italy
* Corresponding Author: Lorenzo Antonuzzo. Email: email
# These authors contributed equally to this work

Oncology Research https://doi.org/10.32604/or.2026.068896

Received 09 June 2025; Accepted 09 October 2025; Published online 13 February 2026

Abstract

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.

Keywords

Metabolomics; biomarkers; bladder cancer (BC); chemotherapy
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