Uncovering novel functions of NUF2 in glioblastoma and MRI-based expression prediction

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.