Gliomas are highly heterogeneous brain tumors with metabolic and molecular alterations that drive their progression and aggressiveness. While genomic classifications have improved glioma diagnosis and prognosis prediction, the functional consequences of tumor progression at the protein and metabolite levels remain not fully explored. This study represents an advancement in glioma research by, for the first time, integrating LC-MS-based proteomics and metabolomics with GC-MS-based metabolomics to comprehensively characterize the molecular landscape of glioma tissues. By capturing key molecular changes occurring between these grades, we identify previously unreported alterations in fundamental pathways, offering a more complete perspective on tumor biology beyond the disturbances that have been only partially explored in earlier studies. Proteomic and metabolomic profiling using LC-MS and GC-MS identified alterations in mitochondrial function, metabolic stress responses, and cytoskeletal remodeling, alongside disruptions in amino acid metabolism, glycolysis, and lipid processing. While confirming known metabolic adaptations in gliomas, our findings also identified previously unreported proteins and metabolites, including plasmalogen alterations (LPC P-18:0, LPC O-18:0), and key metabolic enzymes like TKT and ME1. These insights broaden our understanding of glioma progression, highlighting novel biomarkers and potential therapeutic targets through comprehensive analysis of results from both methods.
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