Sex Disparities in Promoter Methylation and Survival in Glioblastoma: Further Evidence from Clinical Cohorts.

INTRODUCTION

Recent studies suggest an overrepresentation of promoter methylated tumors in females with wt glioblastoma (GBM) compared to males, with a subsequent better response to alkylating treatment.

METHODS

To reveal sex-bound associations that may have gone unnoticed in the original analysis, we re-analyzed two previously published clinical cohorts. One was the multicenter Nordic trial of elderly patients with GBM, randomizing patients into three different treatment arms, including 203 cases with known promoter methylation status. The other was a population-based study of 179 patients with wt GBM, receiving concomittant radiotherapy and chemotherapy with temozolomide. Cohorts were stratified by sex to test the hypothesis that female sex in combination with promoter methylation constitutes a subgroup with more favorable outcome.

RESULTS

There was a significantly larger proportion of promoter methylation and better outcome for female patients with promoter methylated tumors. Results were confirmed in 257 TCGA-derived wt GBM with known sex and status.

CONCLUSIONS

These results confirm that patient sex in combination with promoter methylation is a key determinant in GBM to be considered prior to treatment decisions. Our study also illustrates the need for stratification to identify such sex-bound associations.