Uncovering novel functions of NUF2 in glioblastoma and MRI-based expression prediction
Bibliographic record
Abstract
Glioblastoma multiforme (GBM) is a lethal brain tumor with limited therapies. NUF2, a kinetochore protein involved in cell cycle regulation, shows oncogenic potential in various cancers; however, its role in GBM pathogenesis remains unclear. In this study, we investigated NUF2's function and mechanisms in GBM and developed an MRI-based machine learning model to predict its expression non-invasively, and evaluated its potential as a therapeutic target and prognostic biomarker. Functional assays (proliferation, colony formation, migration, and invasion) and cell cycle analysis were conducted using NUF2-knockdown U87/U251 cells. Western blotting was performed to assess the expression levels of β-catenin and MMP-9. Bioinformatic analyses included pathway enrichment, immune infiltration, and single-cell subtype characterization. Using preoperative T1CE Magnetic Resonance Imaging sequences from 61 patients, we extracted 1037 radiomic features and developed a predictive model using Least Absolute Shrinkage and Selection Operator regression for feature selection and random forest algorithms for classification with rigorous cross-validation. NUF2 overexpression in GBM tissues and cells was correlated with poor survival (p < 0.01). Knockdown of NUF2 significantly suppressed malignant phenotypes (p < 0.05), induced G0/G1 arrest (p < 0.01), and increased sensitivity to TMZ treatment via the β-catenin/MMP9 pathway. The radiomic model achieved superior NUF2 prediction (AUC = 0.897) using six optimized features. Key features demonstrated associations with MGMT methylation and 1p/19q co-deletion, serving as independent prognostic markers. NUF2 drives GBM progression through β-catenin/MMP9 activation, establishing its dual role as a therapeutic target and a prognostic biomarker. The developed radiogenomic model enables precise non-invasive NUF2 evaluation, thereby advancing personalized GBM management. This study highlights the translational value of integrating molecular biology with artificial intelligence in neuro-oncology.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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 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".