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 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 | 0.001 | 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".