MEDU-12. CD271 (P75NTR) AS A NOVEL DIAGNOSTIC MARKER AND THERAPEUTIC TARGET FOR SHH MEDULLOBLASTOMA
Bibliographic record
Abstract
Medulloblastoma (MB) is the most common malignant primary brain tumor and is currently classified into 5 distinct molecular subtypes based on genomic alterations, gene expression profile, response to treatment and cell of origin. This extensive heterogeneity has revealed a critical need for subtype-specific, functionally validated biomarkers and therapeutic strategies. Using an unbiased high throughput flow cytometry screen and gain/loss of function studies, we previously identified CD271/p75NTR as a candidate stem/progenitor cell marker, specifically in SHH MB. Here, we show that CD271+ and CD271- subpopulations do not exhibit a hierarchal organization; but are rather two co-existing cellular subsets. FACS sorting followed by re-culturing of CD271- and CD271+ cells from low passage primary cultures demonstrated that both cell populations can recapitulate the parental phenotype. However, global gene expression profiling by RNA sequencing revealed that genes/pathways associated with cell survival, proliferation and motility are downregulated in CD271- vs. CD271+ subpopulations. Cell cycle analysis supported these findings and demonstrated that CD271- cells exhibited a decrease in proliferation compared to CD271+ cells. Moreover, PI3K/AKT, JAK/STAT, and NFkB, are downregulated in CD271- vs. CD271+ cells, while pathways such as RAS/MYC are upregulated in CD271- vs. CD271+ cells. Immunohistochemical (IHC) analysis of CD271 levels across the MB subtypes demonstrated that nearly all SHH tumors express CD271, while Group 3 tumors exhibit moderate staining. In contrast, Group 4 MB and WNT do not express CD271. Importantly SHH MB exhibit a nodular CD271 staining pattern, further underscoring the heterogeneity within these tumors and supporting our findings that CD271- and CD271+ cells are distinct, yet clinically relevant, subpopulations. Our results suggest that CD271, in combination with other markers, could be effectively utilized as a diagnostic tool for SHH MB and that therapeutic strategies concomitantly targeting both CD271+ and CD271- subpopulations would be the most effective in SHH MB treatment.
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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 | 0.000 |
| 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) | 0.001 | 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".