DNA Tamir Mekanizması İlişkili Genlerin Biyoinformatik Yöntemlerle Glioblastomda Tanımlanması

Abstract

Objective: Aberrant expression of genes involved in DNA repair mechanisms (DRM) have been associated with radiation sensitivity of glioblastoma (GBM) cells. Identification of genes in DRM through bioinformatics methods may help identify potential novel therapeutic targets that can be used in GBM treatment. This study aims to identify genes that play a role in DRM in GBM using bioinformatics methods. Methods: Genes associated with DRM were identified using the “Reactome” and “KEGG” databases. The mRNA expression profiles of DRM related genes were analyzed in the GEO GDS1813 and GDS2853 datasets including GBM tumor samples using the "Orange Canvas" software. Genetic changes of genes were identified in GBM TCGA cases using the cBioPortal database. The GEPIA2 was used to show the effect of altered expression profiles of these genes on patient survival. Results: The mRNA expression profiles of ERCC6, FAN1, MBD4, PARP1 and UNG genes were found to be altered in GBM tumors. Mutations and copy number alterations for the identified genes were observed in TCGA GBM cases. The overall survival and disease-free survival of TCGA GBM patients were not significantly different between high and low expression groups. Conclusion: ERCC6, PARP1 and UNG genes identified in the current study may be potential therapeutic targets that can increase the efficacy of radiotherapy in GBM in case of their suppression.