Gene Expression Signatures Identify Biologically Homogenous Subgroups of Grade 2 Meningiomas
Bibliographic record
Abstract
INTRODUCTION: Meningiomas are the most common brain tumor, with prevalence of approximately 3%. Histological grading has a major role in determining treatment choice and predicting outcome. While indolent grade 1 and aggressive grade 3 meningiomas exhibit relatively homogeneous clinical behavior, grade 2 meningiomas are far more heterogeneous, making outcome prediction challenging. We hypothesized two subgroups of grade 2 meningiomas which biologically resemble either World Health Organization (WHO) grade 1 or WHO grade 3. Our aim was to establish gene expression signatures that separate grade 2 meningiomas into two homogeneous subgroups: a more indolent subtype genetically resembling grade 1 and a more aggressive subtype resembling grade 3. METHODS: Microarray data was analyzed with systems-level gene co-expression network analysis. Fuzzy C-means clustering was employed to reclassify 34 of the 46 grade 2 meningiomas (74%) into a benign "grade 1-like" (13/46), and malignant "grade 3-like" (21/46) subgroup based on transcriptomic profiles. We verified shared biology between matching subgroups based on meta-gene expression and recurrence rates. These results were validated further using an independent RNA-seq dataset with 160 meningiomas, with similar results. RESULTS: Recurrence rates of "grade 1-like" and "grade 3- like" tumors were 0 and 75%, respectively, statistically similar to recurrence rates of grade 1 (17%) and 3 (85%). We also found overlapping biological processes of new subgroups with their adjacent grades 1 and 3. CONCLUSION: These results underpin molecular signatures as complements to histological grading systems. They may help reshape prediction, follow-up planning, treatment decisions and recruitment protocols for future and ongoing clinical trials.
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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) | 0.001 | 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".