CTNNA3 and MBP Mediate Treatment Resistance Through Tumor Microenvironment Remodeling in Recurrent Glioblastoma
Bibliographic record
Abstract
Glioblastoma multiforme represents the most common primary malignant brain tumor in adults, with a 90% 2-year recurrence rate despite standard therapy of surgical resection followed by chemo- and radiotherapy. Yet, the cellular mechanisms underlying therapeutic resistance remain poorly understood. By integrating analysis of single-cell RNA sequencing results of 41 primary and 43 recurrent tumor specimens with experimental validation, we identify neuro-oligodendrocyte precursors as the predominant cellular population driving tumor recurrence through establishment of protective microenvironmental niches. We discover that CTNNA3 and MBP exhibit paradoxical roles in promoting survival in primary tumors while conferring chemoresistance in recurrent GBM, revealing that these factors determine treatment efficacy rather than directly driving relapse. Functional assays confirmed their role as mediators of extracellular matrix remodeling, establishing a mechanistic link between tumor microenvironmental remodeling and therapeutic resistance. By revealing how recurrent tumors engineer self-protective niches, our study provides a new framework for developing combination therapies that disrupt these resistance mechanisms and provides foundation for overcoming treatment failure in this universally fatal disease.
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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 | 0.001 |
| 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".