Upregulation of DNA Metabolism-Related Genes Contributes to Radioresistance of Glioblastoma.

Abstract

Glioblastomas (GBMs) are the most prevalent brain tumor and exhibit poor prognosis. Radiotherapy is an important strategy for GBMs patients; however, this care remains palliative because of GBMs' radioresistance. Glioma stem cells (GSCs), as a subpopulation residing at the apex of the hierarchy, have been believed to be a pivotal population in radioresistance and recurrence of GBMs. To know the key genes involved in radioresistance of GSCs, the gene expression profiles of GSE54660 and GSE60921 were downloaded from Gene Expression Omnibus for genetic and transcriptomic analysis to identify the potential biomarker genes differentially expressed between GSCs and GBMs. These candidate genes were then filtered by the GSCs gene profile responding to radiation and the radioresistant biomarker genes including DNAJC9, GINS2, STAT1, CHAC2, MT1M, and ZNF226 were screened. The differentially expressed genes in GSCs post-irradiation were submitted to Gene Ontology (GO) for further enrichment analysis and protein-protein interaction (PPI) network analysis. A significant module correlated with GINS2 was finally chosen and a series of genes participating in DNA metabolism were identified. In conclusion, this study propounds a set of novel genes that are differentially expressed in the radioresistant subpopulation within GBMs and could serve as promising therapeutic targets.