Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spatially resolved gene expression and tumour-microenvironment interactions across malignant transformation in IDH-mutant glioma

ABSTRACT: Isocitrate dehydrogenase (IDH)-mutant gliomas represent most lower-grade diffuse gliomas in young adults. Although IDH-mutant gliomas initially behave indolently relative to IDH-wildtype counterparts, they undergo inevitable malignant transformation. The mechanisms driving this progression remain poorly defined. We analyzed a rare longitudinal cohort of two patients with IDH-mutant diffuse gliomas, each with matched WHO grade 2, 3, and 4 tumours. Spatial transcriptomics (NanoString GeoMx and 10X Visium), combined with differential expression, spatially variable gene analysis, and gene ontology enrichment, were used to define transcriptional programs underlying progression. Across both patients, higher-grade tumours demonstrated reduced proliferation and a shift toward a migratory, invasive phenotype. Grade 4 samples showed upregulation of genes involved in cell adhesion, axon guidance, cytoskeletal remodeling, and neural development. Spatial analyses localized these programs to tumour invasive margins. GO enrichment highlighted pathways related to neuron projection development, focal adhesion, and lamellipodium organization. Findings were clinically validated using Cox proportional hazards models with LASSO and Elastic Net regularization in a Pan-Cancer Atlas cohort. Elevated expression of invasion-associated genes correlated with shorter progression-free survival and an invasiveness gene signature predicted overall survival . These findings identify candidate molecular drivers of progression and potential targets for timepoint-specific therapeutic intervention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE318238 | GEO | 2026/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Endothelins positively influences the proliferation vs. migration balance of IDH1-mutant glioma cells and promotes proneural to mesenchymal transition

Project description:Adult diffuse gliomas are the deadliest brain tumours including IDH-wildtype glioblastomas of worst prognosis and diffuse low grade IDH-mutant astrocytomas and oligodendrogliomas. These glial tumours display distinct tumoral cell population defeating current therapies. Our group has previously unveiled the role of NOTCH signalling in glioblastoma cell plasticity and in the conversion of oligodendrocytic-like to astrocytic-like tumoral cells in IDH-mutant low-grade gliomas which escalate inevitably to higher grade malignant gliomas. To gain insight into signalling pathways regulating glioma cell plasticity and malignancy, we focused our work on endothelin signalling including endothelin peptide ligands (ET-1, ET-2, ET-3) binding to G-protein coupled endothelin receptors A and B (EDNRA, EDNRB). Here, using glioma patient samples and glioma patient-derived cell lines, we showed that endothelin reduces glioma cell proliferation while increasing migration initiating a proneural to mesenchymal transition. Mechanistically, EDNRB activation led to IP3-dependent calcium mobilization, apamin-sensitive KCNN2/KCNN3 potassium currents and phosphorylation of ERK1/2 and STAT3 in glioma cells. Finally, we studied endothelin receptor regulation by tumoral microenvironment stimuli highlighting a role for EDNRA induced by NOTCH1 and hypoxia in perivascular hypoxic area in glioblastoma. Altogether, this study demonstrates endothelin signalling as a key player in mesenchymal transformation of diffuse IDH-mutant gliomas and glioblastomas.

2026-03-11 | PXD065902 | Pride

Endothelins influences the proliferation-migration balance of IDH1-mutant glioma cells and promotes proneural to mesenchymal transition [RNAseq-Gb7-HUVEC]

Project description:Adult diffuse gliomas are the deadliest brain tumours including IDH-wildtype glioblastomas of worst prognosis and diffuse low grade IDH-mutant astrocytomas and oligodendrogliomas. These glial tumours display distinct tumoral cell population defeating current therapies. Our group has unveiled the role of NOTCH signalling in glioblastoma cell plasticity and in the conversion of oligodendrocytic-like to astrocytic-like tumoral cells in IDH-mutant low-grade gliomas which escalate inevitably to higher grade malignant gliomas. To gain insight into signalling pathways regulating glioma cell plasticity and malignancy, we focused our work on endothelin signalling including endothelin peptide ligands (ET-1, ET-2, ET-3) binding to G-protein coupled endothelin receptors A and B (EDNRA, EDNRB). Here, using glioma patient samples and glioma patient-derived cell lines, we showed that endothelin reduces glioma cell proliferation while increasing migration initiating a proneural to mesenchymal transition. Mechanistically, EDNRB activation led to IP3-dependent calcium mobilization, apamin-sensitive KCNN2/KCNN3 potassium currents and phosphorylation of ERK1/2 and STAT3 in glioma cells. Finally, we studied endothelin receptor regulation by tumoral microenvironment stimuli highlighting a role for EDNRA induced by NOTCH and hypoxia in perivascular hypoxic area in glioblastoma. Altogether, this study demonstrates endothelin signalling as a key player in mesenchymal transformation of diffuse IDH-mutant gliomas and glioblastomas.

2025-09-05 | GSE298358 | GEO

Endothelins influences the proliferation-migration balance of IDH1-mutant glioma cells and promotes proneural to mesenchymal transition [RNAseq-275HCMEC]

Project description:Adult diffuse gliomas are the deadliest brain tumours including IDH-wildtype glioblastomas of worst prognosis and diffuse low grade IDH-mutant astrocytomas and oligodendrogliomas. These glial tumours display distinct tumoral cell population defeating current therapies. Our group has unveiled the role of NOTCH signalling in glioblastoma cell plasticity and in the conversion of oligodendrocytic-like to astrocytic-like tumoral cells in IDH-mutant low-grade gliomas which escalate inevitably to higher grade malignant gliomas. To gain insight into signalling pathways regulating glioma cell plasticity and malignancy, we focused our work on endothelin signalling including endothelin peptide ligands (ET-1, ET-2, ET-3) binding to G-protein coupled endothelin receptors A and B (EDNRA, EDNRB). Here, using glioma patient samples and glioma patient-derived cell lines, we showed that endothelin reduces glioma cell proliferation while increasing migration initiating a proneural to mesenchymal transition. Mechanistically, EDNRB activation led to IP3-dependent calcium mobilization, apamin-sensitive KCNN2/KCNN3 potassium currents and phosphorylation of ERK1/2 and STAT3 in glioma cells. Finally, we studied endothelin receptor regulation by tumoral microenvironment stimuli highlighting a role for EDNRA induced by NOTCH and hypoxia in perivascular hypoxic area in glioblastoma. Altogether, this study demonstrates endothelin signalling as a key player in mesenchymal transformation of diffuse IDH-mutant gliomas and glioblastomas.

2025-09-05 | GSE298357 | GEO

Endothelins positively influences the proliferation vs migration balance of IDH1-mutant glioma cells and promotes proneural to mesenchymal transition [RNAseq-275HUVEC]

Project description:Adult diffuse gliomas are the deadliest brain tumours including IDH-wildtype glioblastomas of worst prognosis and diffuse low grade IDH-mutant astrocytomas and oligodendrogliomas. These glial tumours display distinct tumoral cell population defeating current therapies. Our group has unveiled the role of NOTCH signalling in glioblastoma cell plasticity and in the conversion of oligodendrocytic-like to astrocytic-like tumoral cells in IDH-mutant low-grade gliomas which escalate inevitably to higher grade malignant gliomas. To gain insight into signalling pathways regulating glioma cell plasticity and malignancy, we focused our work on endothelin signalling including endothelin peptide ligands (ET-1, ET-2, ET-3) binding to G-protein coupled endothelin receptors A and B (EDNRA, EDNRB). Here, using glioma patient samples and glioma patient-derived cell lines, we showed that endothelin reduces glioma cell proliferation while increasing migration initiating a proneural to mesenchymal transition. Mechanistically, EDNRB activation led to IP3-dependent calcium mobilization, apamin-sensitive KCNN2/KCNN3 potassium currents and phosphorylation of ERK1/2 and STAT3 in glioma cells. Finally, we studied endothelin receptor regulation by tumoral microenvironment stimuli highlighting a role for EDNRA induced by NOTCH and hypoxia in perivascular hypoxic area in glioblastoma. Altogether, this study demonstrates endothelin signalling as a key player in mesenchymal transformation of diffuse IDH-mutant gliomas and glioblastomas.

2025-09-05 | GSE298356 | GEO

Endothelins influence the proliferation-migration balance of IDH1-mutant glioma cells and promote proneural to mesenchymal transition

Project description:Adult diffuse gliomas are the deadliest brain tumours including IDH-wildtype glioblastomas of worst prognosis and diffuse low grade IDH-mutant astrocytomas and oligodendrogliomas. These glial tumours display distinct tumoral cell population defeating current therapies. Our group has unveiled the role of NOTCH signalling in glioblastoma cell plasticity and in the conversion of oligodendrocytic-like to astrocytic-like tumoral cells in IDH-mutant low-grade gliomas which escalate inevitably to higher grade malignant gliomas. To gain insight into signalling pathways regulating glioma cell plasticity and malignancy, we focused our work on endothelin signalling including endothelin peptide ligands (ET-1, ET-2, ET-3) binding to G-protein coupled endothelin receptors A and B (EDNRA, EDNRB). Here, using glioma patient samples and glioma patient-derived cell lines, we showed that endothelin reduces glioma cell proliferation while increasing migration initiating a proneural to mesenchymal transition. Mechanistically, EDNRB activation led to IP3-dependent calcium mobilization, apamin-sensitive KCNN2/KCNN3 potassium currents and phosphorylation of ERK1/2 and STAT3 in glioma cells. Finally, we studied endothelin receptor regulation by tumoral microenvironment stimuli highlighting a role for EDNRA induced by NOTCH and hypoxia in perivascular hypoxic area in glioblastoma. Altogether, this study demonstrates endothelin signalling as a key player in mesenchymal transformation of diffuse IDH-mutant gliomas and glioblastomas.

2025-09-05 | GSE298282 | GEO

Expression profiling of lower-grade diffuse astrocytic glioma

Project description:Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma (WHO IV), its most malignant subtype, lower-grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notably variable clinical behavior. To examine the foundations of this heterogeneity, we performed multidimensional molecular profiling, including global transcriptional analysis, on 101 lower-grade diffuse astrocytic gliomas collected at our own institution, and validated our findings using publically available gene expression and copy number data from large independent patient cohorts. We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, PDGFRA overexpression, and prolonged survival, and IDH wild-type (IDH wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease outcome. Furthermore, global expression profiling revealed three robust molecular subclasses within lower-grade diffuse astrocytic gliomas, two of which were predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were distinguished from each other on the basis of TP53 mutations, DNA copy number abnormalities, and links to distinct stages of neurogenesis in the subventricular zone (SVZ). This latter finding implicates discrete pools of neuroglial progenitors as cells of origin for the different subclasses of IDH mt tumors. In summary, we have elucidated molecularly distinct subclasses of lower-grade diffuse astrocytic glioma that dictate clinical behavior and demonstrate fundamental associations with both IDH mutational status and neuroglial developmental stage. 80 tumor samples, one normal tissue sample (brain)

2012-02-24 | E-GEOD-35158 | biostudies-arrayexpress

Expression profiling of lower-grade diffuse astrocytic glioma

2012-02-24 | GSE35158 | GEO

Genotyping by array of 297 adult-type diffuse gliomas comprise IDH-mutant astrocytomas, IDH-mutant 1p/19q codeleted oligodendrogliomas, and IDH-wildtype glioblastomas

Project description:Adult-type diffuse gliomas comprise IDH-mutant astrocytomas, IDH-mutant 1p/19q codeleted oligodendrogliomas (ODG), and IDH-wildtype glioblastomas (GBM). GBM display genome instability, which may result from two genetic events leading to massive chromosome alterations: chromothripsis (CT) and whole-genome duplication (WGD). The better prognosis of the latter may be related to their genome stability compared to GBM. Pangenomic profiles of 297 adult diffuse gliomas were analyzed at initial diagnosis using SNP arrays, including 192 GBM and 105 IDH-mutant gliomas (61 astrocytomas and 44 ODG). Tumor ploidy was assessed with Genome Alteration Print and CT events with CTLPScanner and through manual screening.

2024-12-24 | E-MTAB-13542 | biostudies-arrayexpress

Low grade gliomas subtype analysis

Project description:Low grade gliomas (LGG; WHO grade 2 astrocytomas, oligodendrogliomas and oligoastrocytomas) account for about 25% of diffuse gliomas. Most occur in young adults between the ages of 30 and 45 years, and are usually only diagnosed after a seizure. In general, they can be characterised by a long period of continuous slow growth, followed by malignant transformation that will be the cause of death up to 25 years after onset. However, there is a significant number of patients for whom malignant progression is more rapid, with mortality observed within 5 years. This suggests that, as with other tumour types, there may be different subtypes of LGG with specific prognosis. It follows that being able to identify these subtypes may permit better patient stratification and aid targeted treatments. Until recently, our understanding of the variables involved in patient prognosis included the type of tumour oligodendroglial tumours indicate better prognosis than oligoastrocytic or astrocytic and presence of the 1p-19q co-deletion. In addition, the recent discovery of mutations in IDH1&2 in the majority of LGGs provided another means of stratifying patients, while offering an important insight into their biology. However, we still understand very little of the biology behind the genesis and progression of the 70-80% of LGG that bear IDH1&2 mutations, let alone the remaining IDH wild-type tumours.

2015-07-07 | E-MTAB-3708 | biostudies-arrayexpress

Gene expression profile at single level of 8 cell lines isolated from IDH1-mutant diffuse glioma tumors

Project description:Diffuse low-grade gliomas are incurable brain tumours that often carry a mutation in the IDH1 gene. These tumours are heterogeneous and have different types of tumour cells. They can progress toward high grade gliomas. To understand the diversity of tumour cells and how they arise, we have performed single RNA seq of 8 cell lines derived from IDH1 mutant patients. Some cell lines maintained the IDH1 mutation while others lost it. We analysed these cultures when growth factors are present or absent for 4 days to promote differentiation.

2024-05-17 | GSE263796 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data