Involvement of the disulfidptosis-related immune checkpoint gene, CD276, in glioblastoma malignant phenotype and poor prognosis.

Abstract

Background: Immunotherapy has promise for glioblastoma multiforme (GBM) treatment and disulfidptosis, a form of cell death involving disintegration of the actin cytoskeleton, is a potential target. The aim of the current study was to identify genes associated with disulfidptosis-related immune checkpoints in GBM and to analyze connections with malignancy.

Methods: Two expression matrices from The Cancer Genome Atlas-Genotype Tissue Expression (TCGA-GTEx) and Chinese Glioma Genome Atlas (CGGA) cyber public data were utilized to analyze differentially expressed genes (DEGs) in GBM and interaction networks for DEG-coded proteins constructed with protein-protein interaction network analysis. Functional annotation was conducted to indicate DEG function. Hub genes were identified by machine-learning, using Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine Recursive Feature Elimination (SVM-RFE). Gene expression, immune cell composition and single-cell expression were assessed via bioinformatics and in vitro assays. Finally, xenograft nude mouse models were constructed for in vivo validation.

Results: 35 DEGs were found in the TCGA-GTEx and 13 in the CGGA databases and linked to immune regulation and GBM progression. The key gene CD276 was screened by bioinformatics methods. CD276 had higher expression in GBM tissues than in control and was higher expression in GBM strain than in normal astrocytes. In vitro CD276 knockdown reduced GBM cell malignancy. Furthermore, CD276 knockdown suppressed tumor growth in vivo.

Conclusion: CD276 was the most significant hub gene involved in disulfidptosis and immune checkpoints in GBM. Anti-CD276 therapy may have promise for GBM treatment.