Association Between CD204-Expressed Tumor-Associated Macrophages and <i>MGMT</i>-Promoter Methylation in the Microenvironment of Grade 4 Astrocytomas
Bibliographic record
Abstract
Background: Tumor-associated macrophages (TAMs) are principal immune cells in glioma microenvironment which support tumor growth and proliferation. Our aim in this study was to assess the relationship between CD204-expressed TAMs and O 6 -methylguanine-DNA methyltransferase ( MGMT )-promoter methylation in World Health Organization (WHO) grade 4 astrocytomas, and its impact on patient’s clinical outcome. Methods: The expression of CD204 TAMs was quantitively assessed on 45 samples of WHO grade 4 astrocytomas using immunohistochemistry. MGMT -promoter methylation was tested by methylation techniques. The relationship between TAMs, MGMT -promoter methylation, and recurrence-free interval (RFI) was statistically analyzed. Results: There were 10 cases (22.2%) with isocitrate dehydrogenase ( IDH )-mutant grade 4 astrocytoma and 35 cases (77.8%) with IDH -wildtype glioblastoma. MGMT -promotor was methylated in 18 cases (40%), unmethylated in 15 cases (33%), and the remaining 12 cases showed no MGMT status because of nucleic acid degradations. The expression of CD204 + TAMs was high in 32 cases (71.7%) and low in 13 cases (28.8%). The relationship between IDH1 mutation and CD204 + TAM expression was insignificant (P = 0.93). However, the significant difference was found between MGMT methylation and CD204 + TAMs expression (P = 0.01), in which CD204 + TAMs were diffusely expressed in MGMT -methylated cases. There was no significant difference in RFI between CD204 + TAMs expression, MGMT -promoter methylation and treatment modalities. Conclusions: Grade 4 astrocytomas with diffusely expressed CD204 + TAMs are usually associated with MGMT -promoter methylation. Although this association is unclear, CD204 + TAMs may neutralize the effect of MGMT -DNA protein to loss its function, which contributes to tumor progression. This relationship had no significant impact on the patient’s clinical outcome after different treatment modalities. World J Oncol. 2022;13(3):117-125 doi: https://doi.org/10.14740/wjon1473
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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".