523P - Analysis of DNA damage response (DDR) gene expression as a prognostic factor for glioblastoma patient mortality

Background

Glioblastoma (GBM) is associated with an exceptionally poor prognosis with a median survival of 15 months. At present, standard of care involves initial maximal surgical resection, followed by radiotherapy as well as concomitant and adjuvant temozolomide chemotherapy. However, as current therapeutic strategies are insufficient in sterilising tumour cells, GBM represents an area of vital unmet clinical need. Upregulation of DNA damage response (DDR) gene expression in cancer is implicated in tumorigenesis and disease recurrence through the acquisition of driver mutations, evasion of cell death, and reversal of chemotherapy and radiotherapy cytotoxicity. However, DDR gene expression in GBM has not been widely studied. This bioinformatics study aimed to identify DDR genes with expression that is significantly associated with GBM patient survival.

Methods

Clinical and transcriptomic (RNAseq) data from 155 GBM and 4 non-tumour samples using the TCGA-GBM database were subjected to analysis. Kaplan-Meier stratified survival analysis following fitting of the Cox proportional hazard model was conducted on clinical data after stratification based on the median expression of each gene. Multivariate analysis considering the known prognostic significance of age, sex and O6-methylguanine- DNA-methyltransferase (MGMT) promoter methylation status was conducted on gene expression with significant p and q values.

Results

Only 1 out of 298 DDR genes subjected to analysis was significantly associated with patient prognosis after correction for multiple comparisons. This study identified that upregulation of RDM1 gene expression is an independent predictor for detrimental patient prognosis after multivariate analysis in GBM (multivariate HR 1.61, 95% CI 1.03 to 2.51, p = 0.035).

Conclusions

Due to the small proportion of DDR genes with expression significantly associated with prognosis, DDR gene expression is unlikely to be a significant prognostic indicator in GBM patient survival. Further investigation into RDM1 function is warranted to determine the mechanism by which this gene might influence patient outcomes and explore the potential development of novel RDM1-targeted therapies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.