DNA Tamir Mekanizması İlişkili Genlerin Biyoinformatik Yöntemlerle Glioblastomda Tanımlanması

Öz

Amaç: DNA tamir mekanizmalarında (DTM) görev alan genlerin ifade değişimleri glioblastomda (GBM) radyoterapi direnci ile ilişkilendirilmiştir. DTM’de rol oynayan genlerin biyoinformatik yöntemlerle tanımlanması GBM tedavisinde kullanılabilecek potansiyel yeni hedeflerin belirlenmesine yardımcı olabilir. Bu çalışmanın amacı, DNA tamir mekanizmalarında rol oynayan genlerin biyoinformatik yöntemler kullanılarak GBM tümörlerinde tanımlanmasıdır. Yöntem: DNA tamiri mekanizmaları ile ilişkili genler “Reactome” ve “KEGG” veri tabanları üzerinde tanımlandı. GBM tümörlerinde genlere ait mRNA ifade profilleri GEO GDS1813 ve GDS2853 veri setlerinde “Orange Canvas” yazılımı kullanılarak incelendi. Genlerdeki genetik değişimler cBioPortal veri tabanı kullanılarak GBM TCGA olgularında tanımlandı. GEPIA2, değişen gen ifadelerinin TCGA GBM hasta sağ kalım süreleri üzerindeki etkisini göstermek için kullanıldı. Bulgular: ERCC6, FAN1, MBD4, PARP1 ve UNG genlerinin mRNA ifade profillerinin GBM tümörlerinde değişime uğradığı bulundu. Tanımlanan genler için farklı tipte mutasyonlar ve kopya sayı değişimleri TCGA GBM olgularında gözlendi. Yüksek ve düşük gen ifade profillerinin GBM hastalarının genel ve hastalıksız sağ kalım süreleri üzerinde etkisi olmadığı saptandı. Sonuç: Bu çalışmada tanımlanan ERCC6, PARP1 ve UNG genleri baskılanması durumunda GBM’de radyoterapi etkinliğini arttırabilecek potansiyel birer terapötik hedef olabilir.

Anahtar Kelimeler

• Glioblastom
• DNA onarımı
• Biyoinformatik

Identification of Genes Related to DNA Repair Mechanism in Glioblastoma by Bioinformatics Methods

Öz

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.

Anahtar Kelimeler

• Glioblastoma
• DNA repair
• Bioinformatics

Kaynakça

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