AUTHOR=Zhang Qiang , Zhong Hua , Fan Yinchun , Liu Qian , Song Jiancheng , Yao Shengtao , Cao Fang 

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

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2020.00592

DOI=10.3389/fbioe.2020.00592

ISSN=2296-4185

ABSTRACT=<sec><title>Background</title><p>Immune checkpoints target regulatory pathways in T cells that enhance antitumor immune responses and elicit durable clinical responses. As a novel immune checkpoint, <italic>CD96</italic> is an attractive key target for cancer immunotherapy. However, there has been no integrative investigation of <italic>CD96</italic> in glioma. Our study explored the relationship between <italic>CD96</italic> expression and clinical prognosis in glioma.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p><italic>CD96</italic> 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 <italic>CD96</italic> was mostly involved in immune functions and was especially related to T cell-mediated immune response in glioma. Subsequent immune infiltration analysis showed that <italic>CD96</italic> 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, <italic>CD96</italic> was tightly associated with other immune checkpoints, including <italic>PD-1</italic>, <italic>CTLA-4</italic>, <italic>TIGIT</italic>, and <italic>TIM-3</italic>. Univariate and multivariate Cox analysis demonstrated that <italic>CD96</italic> acts as an independent indicator of poor prognosis in glioma.</p></sec><sec><title>Conclusion</title><p><italic>CD96</italic> expression was increased in malignant phenotype and negatively associated with overall survival in glioma. <italic>CD96</italic> also showed a positive correlation with other immune checkpoints, immune response, and inflammatory activity. Our findings indicate that <italic>CD96</italic> is a promising clinical target for further immunotherapeutic use in glioma patients.</p></sec>