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. 2018 Aug 23;7(11):e1461304.
doi: 10.1080/2162402X.2018.1461304. eCollection 2018.

Large-scale analysis reveals the specific clinical and immune features of B7-H3 in glioma

Chaoqi Zhang  1   2 , Zhen Zhang  1 , Feng Li  1 , Zhibo Shen  1   2 , Yamin Qiao  3 , Lifeng Li  1   2 , Shasha Liu  1   2 , Mengjia Song  1   2 , Xuan Zhao  1 , Feifei Ren  1   4 , Qianyi He  1 , Bo Yang  5 , Ruitai Fan  6 , Yi Zhang  1   2   4   7
Affiliations

Large-scale analysis reveals the specific clinical and immune features of B7-H3 in glioma

Chaoqi Zhang et al. Oncoimmunology. .

Abstract

Background: B7-H3 is an immune checkpoint member that belongs to B7-CD28 families and plays a vital role in the inhibition of T-cell function. Importantly, B7-H3 is widely overexpressed on solid tumors, making it become an attractive target for cancer immunotherapy. To clarify the expression panel of B7-H3 in glioma, we explored the clinical and immune features of B7-H3 expression in a large-scale study. Methods and patients: Totally, 1323 glioma samples from Chinese Glioma Genome Atlas (CGGA) dataset, including 325 RNAseq data and 301 mRNA microarray data, and The Cancer Genome Atlas (TCGA) dataset, including 697 RNAseq data, were gathered into our research. The statistical analysis and graphical work were mainly realized by R language. Results: B7-H3 expression was found positively correlated with the grade of malignancy, which might be caused by hypomethylation. The expression level of B7-H3 was consistently up-regulated in IDH wild-type glioma and highly enriched in mesenchymal subtype. GSEA analysis suggested that B7-H3 related genes were more involved in immune response and angiogenesis in glioma. Moreover, B7-H3 showed a consistent positive relationship with stromal and immune cell populations. Further analysis confirmed that B7-H3 played an important role in T-cell-mediated immunity, especially in T-cell-mediated immune response to tumor cell. Circos plots revealed that B7-H3 was tightly associated with most B7 members and other immune checkpoints. Univariate and multivariate cox analysis demonstrated that B7-H3 was an independent prognosticator for glioma patients. Conclusion: B7-H3 represents the malignant phenotype of glioma and independently predicted worse prognosis in glioma patients. Moreover, B7-H3 collaborating with other checkpoint members may contribute to the dysfunctional phenotype of T cell. These findings will be helpful for further optimizing immunotherapies for glioma.

Keywords: B7-H3; CGGA, Chinese Glioma Genome Atlas; CNS, central nervous system; GBM, glioblastoma; HPA, Human Protein Atlas; IDH, isocitrate dehydrogenase; OS, overall survival; TCGA, The Cancer Genome Atlas; glioma; immune checkpoint; immunotherapy; prognosis.

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Figures

Figure 1.
Figure 1.
B7-H3 was significantly enriched in glioblastoma. (A, B, C) B7-H3 was highly expressed in gliolastoma (WHO IV) at transcription level. D B7-H3 was significantly increased in gliolastoma at protein level (HPA017139). *** and **** represent p < 0.001 and p < 0.0001.
Figure 2.
Figure 2.
B7-H3 was consistently up-regulated in IDH wild-type glioma. (A, B, C) B7-H3 was significantly up-regulated in IDH wild-type glioma. (D, E, F) B7-H3 could serve as a biomarker to predict IDH wild-type in glioma. **, *** and **** represent p < 0.01, p < 0.001 and p < 0.0001, respectively.
Figure 3.
Figure 3.
B7-H3 showed a strong expression pattern in mesenchymal molecular subtype glioma. (A, B, C) B7-H3 was highly enriched in mesenchymal molecular subtype glioma. (D, E, F) B7-H3 could serve as a biomarker to predict mesenchymal molecular subtype glioma. *, ** and **** represent p < 0.05, p < 0.01 and p < 0.0001, respectively.
Figure 4.
Figure 4.
B7-H3 related immune genes and signatures in glioma. (A, B) B7-H3 showed a strong positive correlation with most immune genes. (C, D) B7-H3 was closely related to immune response in glioma, especially in T cell mediated immunity. The yellow plots mean the number of genes for each column and the lines mean the tendency of changes in gene number.
Figure 5.
Figure 5.
B7-H3 was tightly associated with immune score and T cell specific immunity. (A and B, upper panel) B7-H3 was positive related with immune score and stromal score. (A and B, lower panel) B7-H3 was closely related to T cell specific immunity.
Figure 6.
Figure 6.
Relationship between B7-H3 and other immune checkpoints. (A, B) Correlation of B7-H3 and other B7 family members. (C, D) Correlation of B7-H3 and other immune checkpoints.
Figure 7.
Figure 7.
Survival analysis of B7-H3 in glioma. (A, B and C) Survival analysis of B7-H3 in whole grade glioma. (D, E and F) Survival analysis of B7-H3 in glioblastoma.
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References

    1. Prosniak M, Harshyne LA, Andrews DW, Kenyon LC, Bedelbaeva K, Apanasovich TV, Heber-Katz E, Curtis MT, Cotzia P, Hooper DC. Glioma grade is associated with the accumulation and activity of cells bearing M2 monocyte markers. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 2013;19:3776–86. - PubMed
    1. Tran B, Rosenthal MA. Survival comparison between glioblastoma multiforme and other incurable cancers. Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia. 2010;17:417–21. - PubMed
    1. Finocchiaro G, Pellegatta S. Immunotherapy for glioma: getting closer to the clinical arena? Curr Opin Neurol. 2011;24:641–7. - PubMed
    1. Mahoney KM, Freeman GJ, McDermott DF. The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma. Clin Ther. 2015;37:764–82. - PMC - PubMed
    1. He J, Hu Y, Hu M, Li B. Development of PD-1/PD-L1 Pathway in Tumor Immune Microenvironment and Treatment for Non-Small Cell Lung Cancer. Sci Rep. 2015;5:13110. - PMC - PubMed

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Grants and funding

This study was supported by the National Key Research and Development Program of China (2016YFC1303501) and the National Natural Science Foundation of China (Grant No. 81771781).