Integrative bioinformatics analysis of the correlation between CDKN2A homozygous deletion, RB1 loss, and PDGFRA amplification in glioma

Introduction: Malignant gliomas constitute a heterogeneous group of primary central nervous system tumors originating from glial cells or their precursors. They display aggressive characteristics and unfavorable clinical outcomes. The 2021 World Health Organization classification emphasizes molecular markers as essential elements for glioma categorization, therapeutic planning, and prognostic assessment. Specific genetic alterations, including CDKN2A homozygous deletion, RB1 loss, and PDGFRA amplification, emerge as potentially crucial determinants of tumor behavior and patient outcomes. Objectives: This investigation examines the relationship between these genetic modifications and survival outcomes while evaluating their influence on the tumor immune landscape. Methods: We utilized the cBioPortal database to analyze the mutation status of CDKN2A homozygous deletion, RB1 loss, and PDGFRA amplification in gliomas, and further investigated the correlation between these mutations and glioma prognosis. Next, we evaluated the expression levels of these genes in gliomas by analyzing data from the Cancer Genome Atlas (TCGA) database. In addition, we explored the potential prognostic value of these genes in gliomas using information from the Chinese Glioma Genome Atlas and TCGA databases. Finally, immunohistochemistry was performed to detect the protein expression of cyclin-dependent kinase inhibitor 2A (CDKN2A), retinoblastoma 1 (RB1), and platelet-derived growth factor receptor alpha (PDGFRA) in gliomas. Results: Our analysis revealed that the homozygous deletion of CDKN2A and the amplification of PDGFRA are significantly correlated with poor overall survival and reduced progression-free survival in glioma patients (p<0.05), while the loss of RB1 showed no significant association with prognosis. Additionally, the expression levels of PDGFRA and RB1 were closely related to immune cell infiltration. Conclusion: High expression of CDKN2A and RB1 generally indicated poorer survival outcomes, whereas elevated expression of PDGFRA exhibited an opposite trend, potentially influencing glioma immune response and therapeutic efficacy by modulating the tumor microenvironment. Immunohistochemical analysis further confirmed the high expression of CDKN2A, RB1, and PDGFRA in gliomas.