PXD065327

PXD065327 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis uncovers enhanced inflammatory pheno-type and distinct metabolic changes in IDH1 mutant glioma cells
Description	Isocitrate dehydrogenase 1 (IDH1) mutations are key drivers of glioma biology, influenc-ing tumor aggressiveness and treatment response. To elucidate their molecular impact, we performed proteome analysis on patient-derived (PD) and U87MG glioma cell models with either mutant or wildtype IDH1. We quantified over 6,000 protein groups per model, identifying 1,594 differentially expressed proteins in PD-AS (IDH1MUT) vs. PD-GB (IDH1WT) and 904 in U87MUT vs. U87WT. Both IDH1MUT models exhibited enhanced MHC antigen presentation and interferon signaling, indicative of an altered immune microen-vironment. However, metabolic alterations were model-dependent: PD-AS cells shifted toward glycolysis and purine salvage, while U87MUT cells retained oxidative phosphory-lation, potentially due to D2-hydroxyglutarate (2OHG)-mediated HIF1A stabilization. We also observed a predominance of downregulated DNA repair proteins in IDH1MUT mod-els, particularly those involved in homologous recombination. In contrast, RB1 and AS-MTL were strongly upregulated in both IDH1MUT models, implicating them in DNA repair and cellular stress responses. We also found distinct expression patterns of proteins reg-ulating histone methylation in IDH1MUT cells, favoring increased methylation of H3K4, H3K9, and H3K36. A key driver of this may be the upregulation of SETD2 in PD-AS, an H3K4 and H3K36 trimethyltransferase linked to recruitment of HIF1A as well as DNA mismatch repair proteins. This study uncovers candidate biomarkers and pathways rele-vant to glioma progression and therapeutic targeting but also underscores the complexity of predicting glioma pathogenesis and treatment responses based on IDH1 mutation sta-tus. While proteome profiling provides valuable insights, a comprehensive understand-ing of IDH1MUT gliomas will likely require integrative multi-omics approaches, including DNA/RNA methylation profiling, histone and protein post-translational modification analyses, and targeted DNA damage and repair assays.
HostingRepository	PRIDE
AnnounceDate	2025-10-06
AnnouncementXML	Submission_2025-10-05_17:42:21.090.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Animesh Sharma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	deamidated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-23 05:27:10	ID requested
⏵ 1	2025-10-05 17:42:22	announced

10.3390/ijms26189075;

Ravn Berg S, Brambilla A, Hagen L, Sharma A, V, å, gb, ø CB, Liabakk NB, Kissova M, Arano Barenys M, Bj, ø, r, å, s M, Torp SH, Slupphaug G, Proteomic Analysis Uncovers Enhanced Inflammatory Phenotype and Distinct Metabolic Changes in IDH1 Mutant Glioma Cells. Int J Mol Sci, 26(18):(2025) [pubmed]

submitter keyword: DNA repair, antigen presentation,Glioma biomarkers, isocitrate dehydrogenase mutations, RNA, DNA and histone demethylases, proteomics, interferon signaling

Geir Slupphaug
contact affiliation	Professor in molecular biology and scientific leader of PROMEC Department of Clinical and Molecular Medicine Faculty of Medicine and Health Sciences +4773598608 +4791825455 +4772573076 Laboratoriesenteret, 231.05.034, Øya, Erling Skjalgssons g 1 Trondheim 7030, Norway
contact email	geir.slupphaug@ntnu.no
lab head
Animesh Sharma
contact affiliation	Engineer at NTNU, Norway
contact email	sharma.animesh@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD065327

PRIDE project URI

• PRIDE
  1. PXD065327
     1. Label: PRIDE project
     2. Name: Proteomic analysis uncovers enhanced inflammatory pheno-type and distinct metabolic changes in IDH1 mutant glioma cells