Comprehensive serum metabolic snapshots enable diagnosis, prognosis, and monitoring for brainstem gliomas [I]

Brainstem gliomas (BSG) is a highly malignant central nervous system childhood tumors with a poor prognosis of a 5-year survival rate of < 10%. Metabolism during radiotherapy is a dynamic and precisely programmed process, improving clinical outcomes and guiding therapy decisions of BSG. Here, we for the first time construct diagnostic and prognostic assays of BSG via circulating metabolites based on both cross-sectional study and longitudinal cohort study with 106 BSG patients. We employ nanoparticle enhanced laser desorption/ionization mass spectrometry to characterize high-resolution static and dynamic snapshots of metabolites during BSG radiotherapy. We show that this serological tool reaches the area under the curve of 0.933 for BSG diagnosis in an independent blind test and predicts risk of patients with significant differences (p < 0.05) in prognostic outcomes. We further identify eight distinct temporal patterns of metabolite regulation associated with radiotherapy responses and tracked the metabolic trajectory via dynamic metabolic snapshots throughout radiotherapy process. If further validated, this framework could be extended to derive comprehensive metabolic pictures for cancers including but not limited to BSG.