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

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.

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.

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.

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.