40 Prognostic significance of PD-L1 expression in meningioma for tumor recurrence; associated with hypoxia and NFKB2 activation
Bibliographic record
Abstract
Estimation of tumor recurrence in meningioma patients is one of the important clinical challenges. The prognostic impact of immune modulatorymolecule PD-L1 in several malignancies has been demonstrated. We studied the association of PD-L1 expression in meningioma with tumor recurrence and the underlying mechanism of its activation. Immunohistochemical staining(IHC) was performed for detection of PD-L1and NFKB2 on whole sections of meningiomas diagnosed between1998-2016 at TorontoWesternHospital. The biologic role of hypoxia in activation of PD-L1 in meningioma was investigated using gene set enrichment analysis(GSEA)-based on RNAseq data in validation cohorts. We analyzed a total of 93 meningioma cases: F/M ratio58/35;WHOgrade I(41),II(43),III(9),42(47%)cases with tumor recurrence and median follow up was 6.97yrs. PD-L1 expression on tumor cells(PD-L1TC) in 33(35%) cases was identified with distinctive patchy distribution. Univariate analysis indicated expression of PD-L1TC as a prognostic factor for tumor recurrence(p<0.0001). Multivariate analysis showed that PD-L1TC expression is an independent prognostic factor for tumor recurrence after adjusting for extent of resection(EOR),WHO grade and maximum tumor diameter(p<0.0001). Analysis of RNAseq data of two GEOmeningioma studies demonstrated prominent expression of NFKB activation associated with PD-L1expression. IHC analysis confirmed increased expression of NFKB2 protein in 26(30%)cases,which correlated with PD-L1TC expression(p=0.02). Furthermore,GSEAon a RNAseq data of 88 sporadic meningiomas using Hypoxia gene signature of HUVEC cells we found that the hypoxic sporadic meningiomas have significantly elevated PD-L1 expression(p<0.001). Our data strongly suggest that PD-L1TCexpression serves as a significant prognostic marker for tumor recurrence and. We found that hypoxia andNFKB2 activation are potential underlying mechanisms. These results also provide a rationale for potential adjuvant therapeutic role for PD-L1 inhibitors in meningioma.
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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 | 0.000 |
| 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) | 0.001 | 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".