Metabolic Profiling of Meningioma Reveals Novel Subgroup-Specific Biologic Insights and Outcome Dependencies
Bibliographic record
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 tumor growth, and therefore poor outcomes, in the so-called hypermetabolic (MG3) tumors, and there is a need to better understand the metabolic landscape of these tumors. This study is the first to study the global metabolon of meningioma in the context of modern molecular subgroups. Methods: Untargeted metabolic profiling (Metabolon Inc.) was performed on 53 meningiomas representing each molecular group 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-mass spectrometry (HPLC-MS/MS). Results: Global metabolic profiling 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) tumors (HR [95% CI] = 6.73 [1.72–6.97], p = 0.006); pyruvate was associated with worse outcomes in proliferative (MG4) tumors 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, surprisingly, better outcomes in the proliferative subgroup. By contrast, upregulated lactate transporters were associated with worse outcomes in proliferative, but not hypermetabolic, meningiomas. Conclusion: 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-MS/MS). In addition, we demonstrated key differences in energy utilization between hypermetabolic and proliferative tumors, both of which are associated with poor outcomes, suggesting fundamental differences in preferred energy utilization and reinforcing a need for subgroup-specific therapies. Publication History Article published online: 07 February 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".