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Proteomic analysis of glioma reveals differentially active pathways among high-grade glioma subgroups

ABSTRACT: Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. Data about proteomics in glioma is sparse and it has not yet been integrated into the routine diagnostic work-up or exploited to find potential actionable targets to prevent GBM-induced immune evasion mechanisms and recurrence. We performed proteomic analysis of diffuse glioma samples classified into six subgroups defined by DNA methylation and patient-paired primary and recurrent samples in order to i) provide an inventory of proteins commonly or individually overexpressed in each of the four HGG subgroups compared to the LGG and deduce relevant pathways for each subgroup and ii) identify specific proteins involved in tumor recurrence after surgical removal. The first study revealed largest differences between low-grade (LGG) and high-grade gliomas (HGG), with major changes observed in proteins involved in active calcium-dependent vesicle trafficking (S100 proteins and annexins), effectors of the immunological synapse, proteins involved in Retinoid acid signalling, and proteins involved in extracellular matrix, cytoskeleton, and cell adhesion. Comparative proteomic analysis between LGG and the HGG subgroups also showed consistency with glioma grading. The second study identified FcGamma receptors on activated microglia and complement components as major players inducing short relapsing GBM tumors. In conclusion, specific pathways and proteins represent potential targets to control progression of the distinct subgroups.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Alexander Schmidt

PROVIDER: MSV000091739 | MassIVE | Wed Apr 19 06:34:00 BST 2023

SECONDARY ACCESSION(S): PXD041647

REPOSITORIES: MassIVE

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