TMET-21. METABOLIC PROFILING OF MENINGIOMA REVEALS NOVEL SUBGROUP-SPECIFIC BIOLOGIC INSIGHTS AND OUTCOME DEPENDENCIES
Bibliographic record
Abstract
Abstract BACKGROUND Prior studies have elucidated the presence of four consensus molecular groups (MGs) of meningioma, with unique underlying biology and outcomes. The hyperactivation of metabolic pathways may be associated with tumour growth in so-called hypermetabolic (MG3) tumours, and there is a need to better understand the metabolic profiles of these tumours. This study is the first to study the global metabolon of meningioma in the context of modern molecular subgroups. METHODS We performed untargeted metabolic profiling of 53 meningiomas representing each MG and WHO grade. Prognostic biochemicals were identified using Cox regression and further investigated using RNA and protein-based pathway analyses. A larger cohort with available RNA sequencing (n=121) was used to further explore the prognostic influence of relevant pathways, and biochemicals of interest were validated on a subset of these samples (n=35) using targeted high performance liquid chromatography (HPLC). RESULTS Our untargeted approach identified 560 unique biochemicals for downstream analysis. The abundance of N6-trimethyllysine was associated with significantly earlier time to recurrence highly prognostic on our whole cohort (HR [95%CI] = 3.18 [1.45-26.23], p = 0.004) and within hypermetabolic (MG3) tumours (HR [95%CI] = 6.73 [1.72-6.97], p = 0.006); pyruvate was with worse outcomes in proliferative (MG4) tumours specifically (HR [95%CI] = 5.65 [1.073-29.71], p = 0.041). Analysis of implicated gene pathways demonstrated that upregulation of the oxidative phosphorylation pathway portends worse outcomes in the hypermetabolic subgroup but better outcomes in the proliferative subgroup. By contrast, upregulated lactate transporters were associated with worse outcomes in proliferative, but not hypermetabolic, meningiomas. CONCLUSIONS This is the first study to demonstrate a subgroup-specific prognostic role of N6-trimethyllysine and pyruvate in meningioma, offering increasingly granular outcome predictions using a widely accessible technique (HPLC). In addition, we demonstrated key differences in energy utilization between hypermetabolic and proliferative tumours suggesting fundamental differences in preferred energy utilization and reinforcing a need for subgroup-specific therapies.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".