PATH-28. DIFFERENCES IN METHYLATION PROFILES BETWEEN LONG-TERM SURVIVORS AND SHORT-TERM SURVIVORS OF IDH WILD-TYPE GLIOBLASTOMA
Bibliographic record
Abstract
Abstract INTRODUCTION Patients with glioblastomas (GBM) have an overall survival (OS) of approximately 15 months. However, approximately 5% of patients survive much longer, with an OS of > 5 years. This study examines the differences in methylation profiles between long-term survivors ( > 5 years, LTS) and short-term survivors (< 1 year, STS) with an isocitrate dehydrogenase (IDH) wild-type GBM. METHODS In a multicenter retrospective analysis, we identified 25 long-term survivors with a histologically confirmed GBM. These were age and sex-matched to a short-term survivor. The methylation profiles of all 50 samples were analyzed with EPIC 850k, classified according to the DKFZ methylation classifier, and the methylation profiles of all IDH wild-type LTS vs STS were compared. RESULTS After methylation profiling, 16/25 LTS and 23/25 STS were confirmed to be IDH wild-type GBMs, all with copy number gains of chromosome 7 and loss of chromosome 10. There were no significant differences between tumour purity or GBM subtype between LTS and STS. LTS had significantly increased MGMT promoter methylation (p = 0.01), and higher FGFR3-TACC3 (p = 0.03), compared to STS. STS had significantly more often a CDKN2A/B loss (p = 0.01) and higher levels of NF1 (p = 0.02), compared to LTS. There were no significant CpGs identified between LTS vs STS at an adjusted p-value of 0.05. Unadjusted analyses identified key pathways and biological processes involved in both LTS and STS. The top pathway in LTS was the Hippo signaling pathway and the Wnt pathway. The top pathway in STS was GPCR ligand binding and cell-cell signaling. CONCLUSION A small group of patients with IDH wild-type GBM survive more than 5 years. While there are few differences in the global methylation profiles of long-term survivors compared to short-term survivors, our study highlights potential pathways involved in aggressive and senescent GBMs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".