CD96 is a promising candidate for immunotherapy. However, its role and importance in glioma remains unknown. We thus aimed to genetically and clinically characterize CD96 expression in gliomas. For this, we extracted RNA-seq data of 699 glioma samples from the TCGA dataset and validated these findings using the CGGA dataset comprising 325 glioma samples. Clinical and isocitrate dehydrogenase (IDH) mutation status were also analyzed. Various packages in R language were mainly used for statistical analysis. CD96 expression was significantly up-regulated in high-grade, IDH-wildtype, and mesenchymal-molecular subtype gliomas based on TCGA data, which was validated using the CGGA dataset. Subsequent gene ontology analysis of both datasets suggested that genes relevant to CD96 are mainly involved in immune functions in glioma as such genes were positively correlated with CD96 expression. To further explore the relationship between CD96 and immune responses, we selected seven immune-related metagenes and found that CD96 expression was positively correlated with HCK, LCK, and MHC II in the CGGA and TCGA cohorts but negatively associated with IgG. Further, Pearson correlation analysis showed that CD96 is associated with TIGIT, CD226, CRTAM, TIM-3, PD-L1, CTLA-4, and STAT3, indicating the additive antitumoral effects of these checkpoint proteins. CD96 was also suggested to play an important role in immune responses and positively collaborate with other checkpoint members. These findings show that CD96 is promising candidate for immunotherapy, and that such agents could complement current immunotherapy strategies for glioma.

CD96是免疫疗法的有希望的候选人。但是，其在神经胶质瘤中的作用和重要性仍然未知。因此，我们旨在在遗传和临床上表征神经胶质瘤中CD96的表达。为此，我们从TCGA数据集中提取了699个神经胶质瘤样本的RNA-seq数据，并使用包含325个神经胶质瘤样本的CGGA数据集验证了这些发现。还分析了临床和异柠檬酸脱氢酶（IDH）突变状态。R语言中的各种软件包主要用于统计分析。根据CGGA数据集验证，基于TCGA数据，高级别，IDH野生型和间充质分子亚型神经胶质瘤中CD96的表达明显上调。随后的两个数据集的基因本体分析表明，与CD96相关的基因主要参与神经胶质瘤的免疫功能，因为这些基因与CD96的表达呈正相关。为了进一步探讨CD96与免疫应答之间的关系，我们选择了七个免疫相关的基因，发现在CGGA和TCGA队列中CD96表达与HCK，LCK和MHC II正相关，而与IgG负相关。此外，Pearson相关分析显示CD96与TIGIT，CD226，CRTAM，TIM-3，PD-L1，CTLA-4和STAT3相关，表明这些检查点蛋白具有累加的抗肿瘤作用。还建议CD96在免疫反应中起重要作用，并与其他检查站成员积极协作。