EPCO-38. IDENTIFYING THE MOLECULAR SIGNATURE OF INFILTRATING EDGE IN GLIOBLASTOMA AS DRIVERS OF TUMOUR INVASION AND RECURRENCE
Bibliographic record
Abstract
Abstract Complete tumour resection in glioblastoma patients is not possible. Residual therapy-resistant edge-derived cells drive tumour recurrence and infiltrative expansion in glioblastoma. Features that are specific to malignant edge-derived cells may serve as predictive biomarkers to allow individual tailoring of the treatment plan to slow down tumour invasion and prevent tumour recurrence in GBM patients following standard therapy. Intratumoural spatial heterogeneity facilitates therapeutic resistance and recurrence in glioblastoma. Our knowledge on glioblastoma heterogeneity is mostly restricted to the surgically resectable tumour core, while the functional characterization of tumour cells at the infiltrating edge remains largely elusive due to the presence of normal functional brain tissue in the peritumoural lesion. Edge-derived cells exhibit larger capacity for infiltrative expansion and are the main drivers of treatment failure and tumour recurrence, making them action targets for novel treatment approaches in glioblastoma. To resolve the transcriptional heterogeneity of GBM within the spatial context, we profiled gene expression of different tumour regions (“edge” and “core”) obtained at initial surgical resection from primary and recurrent IDH-WT GBM patients with Visium 10x and GeoMx. We show that infiltrative edge-derived cells are spatially segregated and are characterized by regionally shared distinct genomic and transcriptomic signatures that promote invasiveness and underly disease recurrence. Tumour edge is enriched for neuronal signatures, while tumour core displays larger transcriptional subpopulation diversity and abundance of proliferative cells with a high capacity for self-renewal, consistent with the proliferative and cancer stem cell-enriched phenotype in early GBM progressors. Upregulated DEGs of tumour edge cells are significantly associated with ion regulation of transport, chemical synaptic transmission, and nervous system development. These modules may represent tumour cell hijacking of neuronal programs specifically at the tumour periphery as described in the context of glioma-neuron synaptic communication and formation of neurite-like microtubes. Upregulation of ion regulation transport at the tumour periphery indicates enhanced neuronal activity and excitability driving infiltrating growth.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".