Abstract
Background Glioma is a common tumor originating from the glial cells of the brain. Immune checkpoint inhibitors can potentially be used to treat gliomas, although no drug is currently approved. Methods The expression levels of the immune checkpoint genes in glioma and normal tissues, and their correlation with the IDH mutation status and complete 1p/19q codeletion, were analyzed using The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. Survival analyses were conducted using the CGGA database. Protein-protein interaction and functional enrichment analyses were performed via the STRING database using GO, KEGG, and Reactome pathways. The correlation between the immune checkpoints and the immune cell infiltration was determined using the TISIDB and TIMER databases. Results HAVCR2 was overexpressed in the gliomas compared to normal brain tissues, as well as in the high-grade glioma patients and significantly downregulated in IDH mutant or 1p/19q codeletion patients. Overexpression of HAVCR2 was associated with poor survival in tumor grades II, III, and IV and was the most correlated with immune infiltration of B and T cells. Conclusion HAVCR2 can be a potential therapeutic target for cancer immunotherapy for glioma patients.
Highlights
Glioma is a common tumor that originates from the glial cells of the brain [1] and accounts for more than 30% of all brain tumors and 80% of the malignant tumors [2]
According to the World Health Organization (WHO) criteria [3], gliomas are classified into the following grades: (i) benign gliomas with relatively low risk that can be removed by surgery depending on their location [4], (ii) low-grade gliomas (LGG) that consist of grades II and III and have highly variable clinical behavior [5], and (iii) glioblastomas (GBM, grade IV) that arise from LGGs and are the most aggressive type [6]
Patients with IDH mutation and complete 1p/19q codeletion generally have a better prognosis compared to the IDH wild-type patients, who might have a different response to therapy [8]
Summary
Glioma is a common tumor that originates from the glial cells of the brain [1] and accounts for more than 30% of all brain tumors and 80% of the malignant tumors [2]. Glioma is a common tumor originating from the glial cells of the brain. The expression levels of the immune checkpoint genes in glioma and normal tissues, and their correlation with the IDH mutation status and complete 1p/19q codeletion, were analyzed using The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. The correlation between the immune checkpoints and the immune cell infiltration was determined using the TISIDB and TIMER databases. HAVCR2 was overexpressed in the gliomas compared to normal brain tissues, as well as in the high-grade glioma patients and significantly downregulated in IDH mutant or 1p/19q codeletion patients. Overexpression of HAVCR2 was associated with poor survival in tumor grades II, III, and IV and was the most correlated with immune infiltration of B and T cells. HAVCR2 can be a potential therapeutic target for cancer immunotherapy for glioma patients
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