Immune and Clinical Features of CD96 Expression in Glioma by in silico Analysis

BACKGROUND: Immune checkpoints target regulatory pathways in T cells that enhance antitumor immune responses and elicit durable clinical responses. As a novel immune checkpoint, CD96 is an attractive key target for cancer immunotherapy. However, there has been no integrative investigation of CD96 in glioma. Our study explored the relationship between CD96 expression and clinical prognosis in glioma. METHODS: RNA and clinical data for a total of 1,001 samples were included in this study, including 325 samples from the Chinese Glioma Genome Atlas (CGGA) database and 676 samples from The Cancer Genome Atlas (TCGA) dataset. The R programming language was employed to perform statistical analysis and draw figures. RESULTS: CD96 had a consistently positive relationship with glioblastoma and was highly enriched in IDH-wildtype and mesenchymal subtype glioma. Gene ontology enrichment and gene set variation analysis analyses suggested that CD96 was mostly involved in immune functions and was especially related to T cell-mediated immune response in glioma. Subsequent immune infiltration analysis showed that CD96 was positively correlated with infiltrating levels of CD4 + T and CD8 + T cells, macrophages, neutrophils, and DCs in glioblastoma multiforme and low-grade glioma. Additionally, CD96 was tightly associated with other immune checkpoints, including PD-1, CTLA-4, TIGIT, and TIM-3. Univariate and multivariate Cox analysis demonstrated that CD96 acts as an independent indicator of poor prognosis in glioma. CONCLUSION: CD96 expression was increased in malignant phenotype and negatively associated with overall survival in glioma. CD96 also showed a positive correlation with other immune checkpoints, immune response, and inflammatory activity. Our findings indicate that CD96 is a promising clinical target for further immunotherapeutic use in glioma patients.