P13.03.B MCM2 HIGHLIGHTS A SUBSET OF AGGRESSIVE MENINGIOMAS WITH ENHANCED PROLIFERATION
Bibliographic record
Abstract
Abstract BACKGROUND While most meningiomas are benign with favorable outcomes, a subset demonstrates high proliferative capacity and follows a lethal clinical course. To predict the postoperative behavior of meningiomas and refine our treatment strategy, we focused on minichromosome maintenance protein 2 (MCM2), a marker of cell proliferation, and investigated the clinical and molecular differences between tumors with high versus low MCM2 immunohistochemical positivity. MATERIAL AND METHODS We performed MCM2 immunohistochemistry on surgical specimens from 36 patients with meningiomas treated at our institution with tumor resection followed by radiotherapy. Cases were dichotomized into MCM2-high and MCM2-low groups based on a 35% positivity cutoff, and progression-free survival (PFS) was compared between groups. In addition, RNA sequencing was conducted in 14 selected cases to assess differences in gene expression profiles between the groups. These findings were validated using public transcriptomic data from the Meningioma (University of Toronto, Nature 2021) cohort. Furthermore, ultrastructural analysis was performed using electron microscopy on high-grade meningioma tissues to investigate intracellular features associated with aggressive behavior. RESULTS The MCM2-high group showed significantly shorter PFS compared to the low group (p < 0.0001), indicating a poorer prognosis. MCM2 mRNA levels were significantly higher in the high group (p = 0.000127), and genes related to cell division and cell cycle regulation were also upregulated. These transcriptomic trends were consistent with findings from the public dataset. These results suggest that elevated MCM2 expression reflects enhanced proliferative activity and contributes to poor clinical outcomes. Additionally, electron microscopy revealed abundant morphologically abnormal mitochondria in high-grade tumors, implying a cancer-like metabolic phenotype. CONCLUSION High MCM2 positivity serves as a surrogate marker for increased mitotic activity and poor prognosis in meningiomas. Moreover, energy metabolism in high-grade meningiomas may align with that of malignant tumors, highlighting a potential therapeutic target. SUPPORT This study was funded by the Japan Society for the Promotion of Science KAKENHI grant (25K18859).
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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 | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.012 | 0.002 |
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".