PXD062733

PXD062733 is an original dataset announced via ProteomeXchange.

Title	Tumor-associated epilepsy and high expression of xCT shape the proteome of IDH-wildtype glioblastoma
Description	Objectives: Epileptogenesis in human glioma is linked to increased glutamate signaling that is primarily facilitated by xCT, suggesting it as a pharmacological target for anti-seizure medication (ASM). Here, we investigated the expression of xCT in glioma-associated epilepsy and investigated the impact of both tumor-associated epilepsy and xCT expression levels on the glioma proteome. Methods: We quantified the expression of xCT and its subunit SLC3A2 by immunoblot in snap-frozen tissue of tumor treatment-naïve IDH-mutant and IDH-wildtype gliomas (n=93) in cases with and without epilepsy (controls)and control cases and compared it to the levels of excitatory amino acid transporter 2 (EAAT2) and the solute carrier family 1 member 4 (SLC1A4). Additionally, we performed whole cell proteomics in IDH-wildtype glioblastoma (GB) from 16 patients with or without epilepsy, and with low or high xCT protein expression. Results: In cases with epilepsy, we observed a trend towards higher expression of xCT and found that EAAT2 and SLC1A4 were significantly higher expressed. Quantitative proteomics of IDH-wildtype GB with epilepsy versus control identified 214 proteins to be significantly regulated. Upregulated proteins showed enrichment for Gene Ontology (GO) terms involving neurotransmitter and amino acid turnover as well as lipid metabolism. Within the epilepsy group, we found a distinction between xCT low- and high-expressing tumors. Of the 231 proteins that were increased in xCT high-expressing tumors, 35 overlapped with proteins upregulated in the epilepsy cohort. These proteins again clustered for GO-BP terms involving neurotransmitter and amino acid metabolism. In addition, xCT high-expressing tumors showed upregulation of proteins that clustered for myelination and regulation of synaptic plasticity. In the survival analysis, epilepsy and high xCT expression did not influence the outcome of patients with either IDH-mutant or IDH-wildtype tumors. Significance: Our results show differences in the proteome of gliomas with and without epilepsyseizures and illustrate that xCT expression levels impact the protein network of these tumors. Our study provides insights into the biological network of these tumors that may be relevant for the development of targeted ASM.
HostingRepository	PRIDE
AnnounceDate	2026-03-21
AnnouncementXML	Submission_2026-03-21_14:39:17.494.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Münch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-08 07:01:36	ID requested
⏵ 1	2026-03-21 14:39:18	announced

10.1038/S41420-026-03029-7;

submitter keyword: human glioma, xCT

Christian Münch
contact affiliation	Goethe University Frankfurt, Institute of molecular systems medicine
contact email	ch.muench@em.uni-frankfurt.de
lab head
Christian Münch
contact affiliation	Goethe University Frankfurt
contact email	ch.muench@em.uni-frankfurt.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062733
     1. Label: PRIDE project
     2. Name: Tumor-associated epilepsy and high expression of xCT shape the proteome of IDH-wildtype glioblastoma