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. 2020 Jun 30:8:592.
doi: 10.3389/fbioe.2020.00592. eCollection 2020.

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

Qiang Zhang  1 , Hua Zhong  2 , Yinchun Fan  1 , Qian Liu  1 , Jiancheng Song  1 , Shengtao Yao  1 , Fang Cao  1
Affiliations

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

Qiang Zhang et al. Front Bioeng Biotechnol. .

Erratum in

Abstract

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.

Keywords: CD96; glioma; immune checkpoint; immunotherapy; prognosis.

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Figures

FIGURE 1
FIGURE 1
Relationship between CD96 expression and clinical glioma parameters in the CGGA and TCGA cohorts. (A,B) Correlation of CD96 transcript levels and WHO grade. (C,D) CD96 expression pattern in different WHO grades. (E,F) Association between CD96 expression and IDH-wildtype for all-grade glioma. (G,H) Correlation of CD96 transcript levels and glioma subtypes. Ns, **, ***, and **** represent no significant, p < 0.05, p < 0.01, and p < 0.0001, respectively.
FIGURE 2
FIGURE 2
CD96 was highly enriched in mesenchymal molecular subtype glioma. (A,B) ROC curve analysis of CD96 in mesenchymal subtype and all-grade gliomas in the CGGA dataset. (C,D) ROC curve analysis of CD96 in mesenchymal subtype and all-grade gliomas in the TCGA dataset.
FIGURE 3
FIGURE 3
Gene ontology (GO) analysis for top 50 genes most relevant to CD96 in the CGGA database (A) and TCGA database (B).
FIGURE 4
FIGURE 4
Heatmaps of CD96-related immune genes in glioma in the CGGA (A) and TCGA cohorts (B).
FIGURE 5
FIGURE 5
CD96-related T cell immunity and immune checkpoint markers in glioma. (A,B) The relationship between CD96 and T cell immunity in glioma in the CGGA and TCGA datasets. (C,D) Corrgram map of CD68 and immune checkpoint markers in glioma in the CGGA and TCGA databases.
FIGURE 6
FIGURE 6
Correlation of CD96 expression with immune infiltration level in GBM and LGG.
FIGURE 7
FIGURE 7
Survival analysis of glioma based on CD96 expression. (A–D) Overall survival analysis of CD96 in all-grade glioma and WHO IV, WHO II, and WHO III gliomas based on data from the CGGA cohort. (E–H) Overall survival analysis of CD96 in all-grade glioma and WHO IV, WHO II, and WHO III gliomas based on data from the TCGA cohort. High and low expressions were defined as the CD96 transcript level being more or less than the median level of all samples.
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