Metabolic signature in patients undergoing adjuvant breast irradiation: a potential for biodosimetry?

This study aims to evaluate metabolic alterations in blood and urine samples from breast cancer patients undergoing adjuvant radiotherapy (RT) to identify potential biomarkers for radiation exposure and contribute to the development of biodosimetry tools, such as for use in nuclear incidents. Postmenopausal breast cancer patients (n = 20) undergoing postoperative RT were included in this prospective observational study. Blood and urine samples were collected at a total of six time points before, during, and after RT. Metabolic analysis was performed using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariable analyses, including partial least squares-discriminant analysis (PLS-DA) and random forest methodology, were used to identify discriminating metabolites. All analyses were performed using R version 4.1.2. Univariate analysis of blood samples showed significant downregulation of five metabolites during RT (week 5 + 6) compared to pre-RT: Hypoxanthine, 3-hydroxyisobutyric acid, L-lactic acid, pyruvic acid and xanthine (all p < .05). No statistically significant changes were found in urine samples. Multivariate analysis using PLS-DA identified a bundle of metabolites associated with radiation exposure, including diverse amino acids, purines, and bile acids. Extreme gradient boosting demonstrated moderate model performance in discriminating irradiated subjects with an AUC of 0.669 in blood samples. This study identified several metabolites altered by RT in blood, providing insight into the metabolic impact of radiation exposure. These findings could provide a basis for developing diagnostic tools to detect radiation exposure. Further studies with larger and more diverse cohorts are needed to validate these biomarkers.