Dataset Information

Identification of Potential Immune Checkpoint Inhibitor Targets in Gliomas via Bioinformatic Analyses.

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.

SUBMITTER: Ding M

PROVIDER: S-EPMC8860561 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Identification of Potential Immune Checkpoint Inhibitor Targets in Gliomas via Bioinformatic Analyses.

Ding Mengmeng M Li Yong-An YA Lu Zhimin Z Hou Guoxin G

BioMed research international 20220214

<h4>Background</h4>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.<h4>Methods</h4>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 ana ...[more]

PMID: 35198632

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Project description:Gliomas are primary tumors that originate in the brain or spinal cord and develop from supportive glial cells. The present study aimed to identify potential candidate molecular markers for the treatment of gliomas, and to explore the underlying mechanisms of this disease. The gene expression profile data GSE50021, which consisted of 10 specimens of normal brain tissues and 35 specimens of glioma tissues, was downloaded from Gene Expression Omnibus (GEO). The methylation microarray data GSE50022, consisting of 28 glioma specimens, was also downloaded from GEO. Differentially expressed genes (DEGs) between patients with glioma and normal individuals were identified, and key methylation sites were screened. Transcriptional regulatory networks were constructed, and target genes were selected. Survival analysis of key methylation sites and risk analysis of sub-pathways were performed, from which key genes and pathways were selected. A total of 79 DEGs and 179 key methylation sites were identified, of which 20 target genes and 36 transcription factors were included in the transcriptional regulatory network. Glutamate metabotropic receptor 2 (GRM2) was regulated by 8 transcription factors. Inositol-trisphosphate 3-kinase A (ITPKA) was a significantly enriched DEG, associated with the inositol phosphate metabolism pathway, Survival analysis revealed that the survival time of patients with lower methylation levels in cg00157228 was longer than patients with higher methylation levels. ITPKA was the closest located gene to cg00157228. In conclusion, GRM2 and enriched ITPKA, associated with the inositol phosphate metabolism pathway, may be key mechanisms in the development and progression of gliomas. Furthermore, the present study provided evidence for an additional mechanism of methylation-induced gliomas, in which methylation results in the dysregulation of specific transcripts. The results of the present study may provide a research direction for studying the mechanisms underlying the development and progression of gliomas.

Project description:BackgroundAdipocyte enhancer binding protein 1 (AEBP1) has been shown to be closely related to cancer progression; however research on its potential role in glioblastoma (GBM) remains limited.MethodsFollowing an expression analysis of AEBP1 in GBM through the Oncomine database, other critical findings were accessed via The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases. Specifically, in addition to identifying differentially expressed genes, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) were further investigated. Additionally, a gene set enrichment analysis (GSEA) was performed to examine the enrichment pathways in the AEBP1 high-expression group. To examine the prognostic role of AEBP1 in GBM, survival information was obtained from the Chinese Glioma Genome Atlas (CGGA) database. Finally, the relationship between the expression of AEBP1 and immune infiltration in GBM was examined by using the "Gene Module", "Survival Module", and "SCNA Module" on the website "Tumor Immune Estimation Resource (TIMER)".ResultsThe Oncomine database revealed that AEBP1 was highly expressed in GBM. The prognostic analyses of 4 independent databases (i.e., TCGA, GTEx, Oncomine, and CGGA) revealed that AEBP1 was an independent predictable marker of GBM. The results of the GSEA showed that protein export, prion disease, cytokine receptor interaction, hematopoietic cell lineage, cell adhesion molecules, apoptosis, and the complement and coagulation cascades were differentially enriched in highly expressed AEBP1 phenotypes. Hence the conclusion is that the high expression of AEBP1 is closely correlated to poor prognosis of GBM. The immune analysis demonstrated that AEBP1 copy number alteration might affect immune infiltration in GBM tissues, and thus the survival outcomes of GBM patients.ConclusionsHigh AEBP1 expression in GBM is closely correlated to patient prognosis. AEBP1 is a potential therapeutic target for the inhibition of cancerous progression and the development of new immunotherapies for GBM.

Dataset Information

Identification of Potential Immune Checkpoint Inhibitor Targets in Gliomas via Bioinformatic Analyses.

Background

Methods

Results

Conclusion

Publications

Identification of Potential Immune Checkpoint Inhibitor Targets in Gliomas via Bioinformatic Analyses.

Similar Datasets

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