High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis
Bibliographic record
Abstract
Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (GBM), is the most malignant brain tumor in adults, with limited therapeutic intervention. Previous studies have identified a few prognostic markers for GBM, including the methylation status of O 6 -methylguanine-DNA methyltransferase ( MGMT ) promoter, TERT promoter mutation, EGFR amplification, and CDKN2A/2B deletion. However, the classification of GBM remains incomplete, necessitating a comprehensive analysis. In this study, we investigated the impact of p16 INK4A expression in GBM and found that p16 INK4A -high GBM exhibits distinct characteristics compared to p16 INK4A -low GBM. Specifically, tumor cells with p16 INK4A -high expression display a senescent phenotype and are correlated with higher intra-tumoral immune cell infiltration. Furthermore, an association was observed between elevated p16 INK4A expression in GBM and extended overall survival of patients. Our in vivo and in vitro studies revealed that CCL13 is predominantly expressed by p16 INK4A -high GBM cells. The released CCL13 enhances the infiltration of T cells within the tumor, potentially contributing to the improved prognosis observed in patients with high p16 INK4A expression. These findings suggest that tumor cells with a senescence phenotype in GBM, through the secretion of chemokines such as CCL13, may augment immune cell infiltration and potentially enhance patient outcomes by creating a more immunologically active tumor microenvironment.
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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) | 0.000 | 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) | 0.000 | 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".