A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas

Simple Summary Since the publication in 2016 of the WHO's classification of primary brain tumors according to their histopathology but also their molecular status (IDH, 1p/19q codeletion), oligodendrogliomas defined by the presence of the 1p/19q codeletion have been clearly identified as having a better prognosis. However, the response to treatment of 1p/19q codeleted gliomas remains heterogeneous. Very few studies have investigated the genetic profiles of these tumors, particularly with regard to their response to treatment (radiotherapy and chemotherapy). Our analyses revealed a gene signature composed of eight genes involved in metabolism, immunity, and extracellular matrix organization pathways that were associated with a poor response to treatment for 1p/19q codeleted tumors. This signature could be used in the future to identify patients who need more intensive treatment, potentially with inhibitors of these pathways. Background. IDH mutant and 1p/19q codeleted oligodendrogliomas are the gliomas associated with the best prognosis. However, despite their sensitivity to treatment, patient survival remains heterogeneous. We aimed to identify gene expressions associated with response to treatment from a national cohort of patients with oligodendrogliomas, all treated with radiotherapy +/- chemotherapy. Methods. We extracted total RNA from frozen tumor samples and investigated enriched pathways using KEGG and Reactome databases. We applied a stability selection approach based on subsampling combined with the lasso-pcvl algorithm to identify genes associated with progression-free survival and calculate a risk score. Results. We included 68 patients with oligodendrogliomas treated with radiotherapy +/- chemotherapy. After filtering, 1697 genes were obtained, including 134 associated with progression-free survival: 35 with a better prognosis and 99 with a poorer one. Eight genes (ST3GAL6, QPCT, NQO1, EPHX1, CST3, S100A8, CHI3L1, and OSBPL3) whose risk score remained statistically significant after adjustment for prognostic factors in multivariate analysis were selected in more than 60% of cases were associated with shorter progression-free survival. Conclusions. We found an eight-gene signature associated with a higher risk of rapid relapse after treatment in patients with oligodendrogliomas. This finding could help clinicians identify patients who need more intensive treatment.

Automated summary

Since the WHO's classification of primary brain tumors in 2016, oligodendrogliomas with the 1p/19q codeletion have been identified as having a better prognosis. However, the response to treatment for these tumors remains heterogeneous. Our study identified a gene signature composed of eight genes that were associated with a poor response to treatment in 1p/19q codeleted tumors. This signature could be used to identify patients who require more intensive treatment.