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

Authors

Zhong RD,Liu YS,Li Q,Kou ZW,Chen FF,Wang H,Zhang N,Tang H,Zhang Y,Huang GD

Affiliations (8)

  • Department of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, P.R. China.
  • Guangdong Provincial Key Laboratory for Regional Immunity and Diseases, Department of Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, P.R. China.
  • Cancer Center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, 518000, P.R. China.
  • Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P.R. China.
  • Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
  • Department of Neurosurgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, P.R. China. [email protected].
  • Department of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, P.R. China. [email protected].
  • Department of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, P.R. China. [email protected].

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.

Topics

GlioblastomaMagnetic Resonance ImagingBrain NeoplasmsCell Cycle ProteinsJournal Article

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