Dataset Information

Identification of Aberrantly Expressed Genes in Murine Glioblastoma During Radiotherapy via Bioinformatic Data Mining.

ABSTRACT: Objective:Glioblastoma (GBM) is an aggressive tumor with a fast growth rate. Radioresistance of GBM can lead to high recurrence. In general, due to the protection of the blood-brain barrier, the immune environment of the central nervous system is unique. The immune response induced by radiotherapy is weak in GBM. In the present study, aberrantly expressed genes during radiotherapy were assessed in murine models based on microarray RNA data. Methods:The microarray data were extracted from the Intergovernmental Group on Earth Observations and differentially expressed genes (DEGs) screened out. Gene expression profiles of 115 samples in GSE56113 were analyzed and 104 genes were identified as aberrantly expressed based on GEO2R 8 d after radiotherapy. Then, the Database for Annotation, Visualization, and Integrated Discovery was used to analyze Genome Kyoto Encyclopedia of Gene pathways and Gene Ontology (GO) terms. The 20 core candidate genes were identified using protein-protein interaction network analysis and Cytoscape software with Molecular Complex Detection plug-in. Results:Post-irradiated tumor tissues expressed significantly more immune-associated genes than contralateral brain tissues. GO and pathway analyses showed core DEGs were mainly enriched in the chemokine signaling and IL-6 signaling pathways, which could lead to immunosuppressive inflammatory monocyte infiltration and radioresistance. Chemokine signaling and IL-6 signaling pathway-associated genes were increased in the irradiated U87 cell strain. Conclusion:Chemokine signaling and IL-6 signaling pathways were activated after radiation in murine glioma and human glioma cell lines which could lead to changes in the immune microenvironment and treatment failure. The results of the present study could provide potential therapeutic targets especially when immune therapy and radiotherapy are combined to treat GBM patients.

SUBMITTER: Zhao X

PROVIDER: S-EPMC7212782 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of Aberrantly Expressed Genes in Murine Glioblastoma During Radiotherapy via Bioinformatic Data Mining.

Zhao Xihe X Zhao Xihe X Li Chenxi C Liu Lei L Zou Huawei H Li Kai K

OncoTargets and therapy 20200506

<h4>Objective</h4>Glioblastoma (GBM) is an aggressive tumor with a fast growth rate. Radioresistance of GBM can lead to high recurrence. In general, due to the protection of the blood-brain barrier, the immune environment of the central nervous system is unique. The immune response induced by radiotherapy is weak in GBM. In the present study, aberrantly expressed genes during radiotherapy were assessed in murine models based on microarray RNA data.<h4>Methods</h4>The microarray data were extract ...[more]

PMID: 32440151

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Project description:Glioblastoma multiforme (GBM) is the most malignant primary tumour type of the central nervous system with limited therapeutic options and poor prognosis, and its pathogenic mechanisms have remained to be fully elucidated. Aberrant DNA methylation is involved in multiple biological processes and may contribute to the occurrence and development of GBM by affecting the expression of certain genes. However, the specific molecular mechanisms remain to be fully elucidated. The present study focused on uncovering differentially expressed genes with altered methylation status in GBM and aimed to discover novel biomarkers for the diagnosis and treatment of GBM. These genes were identified by combined analysis of multiple gene expression and methylation datasets from gene expression omnibus (GSE16011, GSE50161 and GSE 50923) to increase the reliability. In addition, The Cancer Genome Atlas (TCGA) dataset for GBM was used to test the stability of the results. Overall, 251 hypomethylated upregulated genes (Hypo-UGs) and 199 hypermethylated downregulated genes (Hyper-DGs) were identified in the present study. Functional enrichment analysis revealed that the Hypo-UGs are involved in the regulation of immune- and infection-associated signalling, while the Hyper-DGs are involved in the regulation of synaptic transmission. The three hub genes for Hyper-DGs (somatostatin, neuropeptide Y and adenylate cyclase 2) and five hub genes for Hypo-UGs [interleukin-8, matrix metalloproteinase (MMP)9, cyclin-dependent kinase 1, 2'-5'-oligoadenylate synthetase 1, C-X-C motif chemokine ligand 10 and MMP2] were identified by protein-protein interaction network analysis. Among the Hypo-UGs and Hyper-DGs, overexpression of C-type lectin domain containing 5A, epithelial membrane protein 3, solute carrier family 43 member 3, STEAP3 metalloreductase, tumour necrosis factor α-induced protein 6 and apolipoprotein B mRNA editing enzyme catalytic subunit 3G was significantly associated with poor prognosis in the TCGA and GSE16011 datasets (P<0.001). In conclusion, the present study uncovered numerous novel aberrantly methylated genes and pathways associated with GBM. Methylation-based markers, including the hub genes and prognostic genes identified, may potentially serve as markers for the diagnosis of GBM and targets for its treatment.

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Dataset Information

Identification of Aberrantly Expressed Genes in Murine Glioblastoma During Radiotherapy via Bioinformatic Data Mining.

Publications

Identification of Aberrantly Expressed Genes in Murine Glioblastoma During Radiotherapy via Bioinformatic Data Mining.

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