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.
import lamindb as ln
import spatialdata as sd
coll = ln.Collection.get(key="geo-gse318238")
coll.ordered_artifacts.df() # the 3 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]
# …or load each straight into memory as a SpatialData object:
sdatas = {a.key: sd.read_zarr(a.cache()) for a in coll.ordered_artifacts.all()}
Visium 
Visium 
Visium No linked publication found — please cite the data source.