Dataset Information

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

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.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC7338376 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Immune and Clinical Features of <i>CD96</i> Expression in Glioma by <i>in silico</i> Analysis.

Zhang Qiang Q Zhong Hua H Fan Yinchun Y Liu Qian Q Song Jiancheng J Yao Shengtao S Cao Fang F

Frontiers in bioengineering and biotechnology 20200630

<h4>Background</h4>Immune checkpoints target regulatory pathways in T cells that enhance antitumor immune responses and elicit durable clinical responses. As a novel immune checkpoint, <i>CD96</i> is an attractive key target for cancer immunotherapy. However, there has been no integrative investigation of <i>CD96</i> in glioma. Our study explored the relationship between <i>CD96</i> expression and clinical prognosis in glioma.<h4>Methods</h4>RNA and clinical data for a total of 1,001 samples wer ...[more]

PMID: 32695752

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Project description:BackgroundImmunotherapy has significantly improved patient outcomes, but encountered obstacles recently. CD96, a novel immune checkpoint expressed on T cells and natural killer (NK) cells, is essential for regulating immune functions. However, how CD96 correlating with immune infiltration and patient prognosis in pan-cancer remains unclear.MethodsHPA, TCGA, GEO, GTEx, Oncomine, TIMER2.0, PrognoScan, Linkedomics, Metascape, and GEPIA2 databases were used to analyze CD96 in cancers. Visualization of data was mostly achieved by R language, version 4.0.2.ResultsIn general, CD96 was differentially expressed between most cancer and adjacent normal tissues. CD96 significantly impacted the prognosis of diverse cancers. Especially, high CD96 expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) in the TCGA lower grade glioma (LGG) cohort (OS, HR = 2.18, 95% CI = 1.79-2.66, P < 0.001). The opposite association was significantly observed in skin cutaneous melanoma (SKCM) cohort (OS, HR = 0.96, 95% CI = 0.94-0.98, P < 0.001). Notably, SKCM samples demonstrated the highest CD96 mutation frequency among all cancer types. Furthermore, in most cancers, CD96 expression level was significantly correlated with expression levels of recognized immune checkpoints and abundance of multiple immune infiltrates including CD8+ T cells, dendric cells (DCs), macrophages, monocytes, NK cells, neutrophils, regulatory T cells (Tregs), and follicular helper T cells (Tfh). CD96 was identified as a risk factor, protective factor, and irrelevant variable in LGG, SKCM and adrenocortical carcinoma (ACC), respectively. CD96 related genes were involved in negative regulation of leukocyte in LGG, however, involved in multiple positive immune processes in SKCM. Furthermore, CD96 was significantly associated with particular immune marker subsets. Importantly, it strongly correlated with markers of type 1 helper T cell (Th1) in SKCM, but not in LGG or ACC either.ConclusionsCD96 participates in diverse immune responses, governs immune cell infiltration, and impacts malignant properties of various cancer types, thus standing as a potential biomarker for determining patient prognosis and immune infiltration in multiple cancers, especially in glioma and melanoma.

Project description:Background: As immunotherapy of oral squamous cell carcinomas (OSCCs), using PD1 inhibitors, is only efficient in a small proportion of patients, additional immune checkpoints need to be identified as potential therapeutic targets. There is evidence that a blockade of CD96 might positively affect the anti-tumor immune response. The aim of this study was to analyze the gene and protein expression of CD96 in the tissue and peripheral blood of OSCC patients compared to healthy controls, while also checking for potential associations with a differential expression to the histomorphological parameters. In addition, possible correlations with the expression of PD1 and PD-L1 as well as the macrophage markers CD68 and CD163 should be tested to obtain further insights into the potential effectiveness of combined checkpoint blockage. Material and Methods: For real-time quantitative polymerase chain reaction (RT-qPCR), a total of 183 blood and tissue samples, divided into a patient and a control group, were included. Additionally, 141 tissue samples were examined by immunohistochemistry (IHC). The relative expression differences between the groups were calculated using statistical tests including the Mann-Whitney U test and AUC method. The Chi-square test was used to determine whether CD96 overexpression in individual samples is associated with malignancy. Correlation analysis was performed using the Spearman correlation test. Results: There was a significant CD96 mRNA and protein overexpression in the OSCC group compared to the controls (p = 0.001). In contrast, CD96 mRNA expression in the peripheral blood of the OSCC patients was significantly lower compared to the control group (p = 0.007). In the Chi-square test, the OSCC tissue samples showed a highly significant upregulation of CD96 mRNA expression (p < 0.001) and protein expression (p = 0.005) compared to the healthy mucosa. CD96 mRNA and protein expression correlated significantly (p = 0.005). In addition, there was a significant positive correlation of CD96 expression with PD1 (p ≤ 0.001), PD-L1 (p ≤ 0.001), and CD163 (p = 0.006) at the mRNA level. Conclusions: CD96 expression in the tumor tissue and peripheral blood of OSCC patients is differentially regulated and appears to be a relevant immune checkpoint.

Dataset Information

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

Publications

Immune and Clinical Features of <i>CD96</i> Expression in Glioma by <i>in silico</i> Analysis.

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