Abstract
Cancer cells have altered cellular metabolism. Mutations in genes associated with key metabolic pathways (e.g., isocitrate dehydrogenase 1 and 2, IDH1/IDH2) are important drivers of cancer, including central nervous system (CNS) tumors. Therefore, we hypothesized that the abnormal metabolic state of CNS cancer cells leads to abnormal levels of metabolites in the CSF, and different CNS cancer types are associated with specific changes in the levels of CSF metabolites. To test this hypothesis, we used mass spectrometry to analyze 129 distinct metabolites in CSF samples from patients without a history of cancer (n = 8) and with a variety of CNS tumor types (n = 23) (i.e., glioma IDH-mutant, glioma-IDH wildtype, metastatic lung cancer and metastatic breast cancer). Unsupervised hierarchical clustering analysis shows tumor-specific metabolic signatures that facilitate differentiation of tumor type from CSF analysis. We identified differences in the abundance of 43 metabolites between CSF from control patients and the CSF of patients with primary or metastatic CNS tumors. Pathway analysis revealed alterations in various metabolic pathways (e.g., glycine, choline and methionine degradation, dipthamide biosynthesis and glycolysis pathw...Continue Reading
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