NMR metabolomics in bladder cancer: Identification and monitoring of serum biomarkers during Pt-based treatment.

Abstract

3057 Background: To date, predictive and prognostic biomarkers for Bladder Cancer (BC) are lacking. Metabolomics, the study of small molecules involved in metabolism, aims to identify diagnostic, predictive and prognostic biomarkers. Overall, BC shows perturbations of various metabolic pathways, involved in biochemical reactions essential for energy production and for the maintenance of the REDOX balance, as well as in the metabolism of purines and pyrimidines. The main objective of this study is to characterize the serum metabolic profile of patients with BC undergoing platinum-based chemotherapy (Pt-CT), to identify the alterations induced by CT and evaluate the associated deregulated metabolic pathways, in order to identify potential biomarkers, prognostic and predictive of response to treatment. Methods: We enrolled patients with BC undergoing Pt-CT in different settings (neoadjuvant, adjuvant or metastatic). For each patient, a blood sample was collected before the start of each CT cycle (T0, T1, Tn). Metabolomic analysis was performed using the Bruker Avance 600 spectrometer. At baseline (T0), the metabolomic profiles of BC patients were compared with that of age- and sex-matched healthy controls. Major metabolites up- or down-regulated in patients with BC at baseline, were then monitored during CT (T1, Tn). Results: 14 patients were enrolled. When compared with age- and sex-matched healthy controls, patients with BC had elevated levels of acetate and acetone (ketone bodies), hypoxanthine, trimethylamine N-oxide (TMAO), glutamate, lactate, phenylalanine, and ornithine, and decreased levels of carnitine, choline, betaine, aspartate, threonine, 2-hydroxybutyrate, 2-aminobutyrate and histidine. When monitored during CT, hypoxanthine, glutamate, and aspartate levels increased; acetone, acetate and TMAO instead had a decreasing trend. Conclusions: The results of our pilot study confirm perturbations in several metabolic pathways: up-regulation of lactate, ketone bodies, hypoxanthine, phenylalanine, and glutamate levels in BC patients reflects altered glycolysis, fatty acid, purine, and amino acid metabolism, respectively. In addition, TMAO may play a role in the development of BC by promoting a pro-inflammatory and oxidative stress state. Furthermore, monitoring these metabolites could be a useful tool for predicting response to treatments. To our knowledge, there are no metabolomic studies that evaluated BC patients receiving CT and that included longitudinal monitoring to identify any changes in the metabolic profile induced by treatment.