Immune and Clinical Features of CD96 Expression in Glioma by in silico Analysis
Immune and Clinical Features of CD96 Expression in Glioma by in silico Analysis
复制标题
胶质瘤中 CD96 表达的免疫和临床特征的计算机分析
DOI：
10.3389/fbioe.2020.00592
复制
发表时间：
2020-06-30
影响因子：
5.7
通讯作者：
Cao, Fang
中科院分区：
文献类型：
--
作者：
Zhang, Qiang;Zhong, Hua;Cao, Fang
免疫检查点靶向T细胞中的调节途径，其增强抗肿瘤免疫应答并引起持久的临床应答。CD 96作为一种新的免疫检查点，是肿瘤免疫治疗的重要靶点。然而，目前对CD 96在胶质瘤中的表达尚缺乏系统的研究。本研究旨在探讨CD 96在胶质瘤中的表达与临床预后的关系。方法选取中国胶质瘤基因组图谱（CGGA）数据库中325例和美国肿瘤基因组图谱（TCGA）数据库中676例标本，共1,001例标本的RNA和临床资料。采用R程序设计语言进行统计分析和绘图。结果CD 96与胶质母细胞瘤呈一致性正相关，在IDH野生型和间质亚型胶质瘤中高度富集。基因本体富集和基因集变异分析表明，CD 96主要参与胶质瘤的免疫功能，尤其与T细胞介导的免疫应答有关。随后的免疫浸润分析显示，在多形性胶质母细胞瘤和低级别胶质瘤中，CD 96与CD 4 + T和CD 8 + T细胞、巨噬细胞、中性粒细胞和DC的浸润水平呈正相关。此外，CD 96与其他免疫检查点密切相关，包括PD-1、CTLA-4、TIGIT和TIM-3。单因素和多因素考克斯分析表明，CD 96是胶质瘤预后不良的独立指标。结论CD 96在胶质瘤恶性表型中表达增高，与总生存期呈负相关，与其他免疫检查点、免疫应答和炎症活动呈正相关。我们的研究结果表明，CD 96是一个有前途的临床目标，进一步免疫治疗胶质瘤患者。
Background Immune checkpoints target regulatory pathways in T cells that enhance antitumor immune responses and elicit durable clinical responses. As a novel immune checkpoint,CD96is an attractive key target for cancer immunotherapy. However, there has been no integrative investigation ofCD96in glioma. Our study explored the relationship betweenCD96expression 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 CD96had 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 thatCD96was mostly involved in immune functions and was especially related to T cell-mediated immune response in glioma. Subsequent immune infiltration analysis showed thatCD96was positively correlated with infiltrating levels of CD4 + T and CD8 + T cells, macrophages, neutrophils, and DCs in glioblastoma multiforme and low-grade glioma. Additionally,CD96was tightly associated with other immune checkpoints, includingPD-1,CTLA-4,TIGIT, andTIM-3. Univariate and multivariate Cox analysis demonstrated thatCD96acts as an independent indicator of poor prognosis in glioma. Conclusion CD96expression was increased in malignant phenotype and negatively associated with overall survival in glioma.CD96also showed a positive correlation with other immune checkpoints, immune response, and inflammatory activity. Our findings indicate thatCD96is a promising clinical target for further immunotherapeutic use in glioma patients.