Metabolomics-Based Biosignatures of Prostate Cancer in Patients Following Radiotherapy

Metabolomics offers new promise for research on prostate cancer (PCa) and its personalized treatment. Metabolomic profiling of radiation-treated PCa patients is particularly important to reveal their new metabolomic status, and evaluate the radiation effects. In addition, bioinformatics-integrated metabolomics-based approaches for disease profiling and assessment of therapy could help develop precision biomarkers in a context of PCa. We report mass spectrometry-based untargeted (global) serum metabolomics findings from patients with PCa (n = 55) before and after treatment with stereotactic body radiation therapy (SBRT), and intensity-modulated radiation therapy (IMRT) with SBRT, and using parsimony phylogenetic analysis. Importantly, the radiation-treated serum metabolome of patients represented a unique robust cluster on a cladogram that was distinct from the pre-RT metabolome. The altered radiation responsive serum metabolome was defined by predominant aberrations in the metabolic pathways of nitrogen, pyrimidine, purine, porphyrin, alanine, aspartate, glutamate, and glycerophospholipid. Our findings collectively suggest that global metabolomics integrated with parsimony phylogenetics offer a unique and robust systems biology analytical platform for powerful unbiased determination of radiotherapy (RT)-associated biosignatures in patients with PCa. These new observations call for future translational research for evaluation of metabolomic biomarkers in PCa prognosis specifically, and response to radiation treatment broadly. Radiation metabolomics is an emerging specialty of systems sciences and clinical medicine that warrants further research and educational initiatives.