Gene Expression Associated with Drug Response Variation of Temozolomide and Clinical Outcomes in Glioma Patients.

Temozolomide (TMZ) chemotherapy is an important tool in the treatment of glioma brain tumors. However, variable patient response and chemo-resistance remain exceptionally challenging. Our previous genome-wide association study (GWAS) identified a suggestively significant association of SNP rs4470517 in the (receptor-like kinase) gene with TMZ drug response. Functional validation of using lymphocytes and glioma cell lines resulted in gene expression analysis indicating differences in expression status between genotypes of the cell lines and TMZ dose response. We conducted univariate and multivariate Cox regression analyses using publicly available TCGA and GEO datasets to investigate the impact of gene expression status on glioma patient overall (OS) and progression-free survival (PFS). Our results indicated that in mutant gliomas, expression and tumor grade were significant predictors of survival. In wildtype glioblastomas (GBM), status was the only significant predictor. Despite this result, we revealed a potential benefit of expression in wildtype GBM patients. We found that a combination of expression and status could serve as an additional biomarker for improved survival. Overall, our findings suggest that expression may serve as an important prognostic or predictor of TMZ response and survival for glioma patients.