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Genetic and clinical characterization of B7-H3 (CD276) expression and epigenetic regulation in diffuse brain glioma

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机构： [1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China [2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China [3]Chinese Glioma Genome Atlas network, Beijing, China [4]Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China [5]China National Clinical Research Center for Neurological Diseases, Beijing, China

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关键词： B7-H3 checkpoint inhibitors glioma immune response outcome

摘要：

Gliomas are the most common malignant tumors of the brain. Immune checkpoints have been increasingly emphasized as targets for treating malignant tumors. B7-H3 has been identified as an immune checkpoint that shows potential value for targeting therapies. We set out to characterize the expression pattern and biological function of B7-H3 in brain gliomas using high-throughput data obtained from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) projects. B7-H3 was upregulated more in higher-grade gliomas than that in lower-grade gliomas in both CGGA and TCGA datasets. Isocitrate dehydrogenase (IDH) mutation seemed to exert significant influence on B7-H3 expression in gliomas but led to quite different results between grade II gliomas and higher-grade gliomas. In addition to IDH, methylation of B7-H3 promoter and microRNA-29 family also showed a potential regulatory effect on B7-H3 expression. Gene ontology analysis revealed that B7-H3 was associated with mitotic cell cycle, cell proliferation and immune response. Further investigation suggested that B7-H3 was mostly involved in the Toll-like receptor signaling pathway. Survival analysis indicated that B7-H3 was an independent unfavorable prognosticator for glioma patients in both CGGA and TCGA datasets. B7-H3 expression is regulated by multiple mechanisms and is potentially involved in the T-cell receptor signaling pathway. Higher B7-H3 expression indicates a worse prognosis for glioma patients, which warrants further research into the development of inhibitors for targeting this immune checkpoint, but we still need to be cautious about immune checkpoint inhibition for central nervous system tumors.

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中科院(CAS)分区：

出版当年[2017]版：

大类 | 2 区医学

小类 | 3 区肿瘤学

最新[2023]版：

大类 | 2 区

医学

小类 | 2 区肿瘤学

JCR分区：

出版当年[2016]版：

Q2 ONCOLOGY

最新[2023]版：

Q1 ONCOLOGY

影响因子： 4.5 最新[2023版] 5.5 最新五年平均 3.974 出版当年[2016版] 3.757 出版当年五年平均 3.896 出版前一年[2015版] 4.372 出版后一年[2017版]

第一作者：

第一作者机构： [1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China [2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China [3]Chinese Glioma Genome Atlas network, Beijing, China

通讯作者：

通讯机构： [1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China [2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China [3]Chinese Glioma Genome Atlas network, Beijing, China [4]Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China [5]China National Clinical Research Center for Neurological Diseases, Beijing, China [*1]Department of Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, No. 6, Tiantan Xili, Doncheng District, Beijing 100050, China.

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Genetic and clinical characterization of B7-H3 (CD276) expression and epigenetic regulation in diffuse brain glioma

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