Transcription factor networks of oligodendrogliomas treated with adjuvant radiotherapy or observation inform prognosis

Abstract

Background: Recent international sequencing efforts have allowed for the molecular taxonomy of lower-grade gliomas (LGG). We sought to analyze The Cancer Genome Atlas (TCGA, 2015) gene expression datasets on molecularly defined oligodendrogliomas (IDH-mutated and 1p/19q-codeleted) patients treated with adjuvant radiation or those observed to discover prognostic markers and pathways.

Methods: mRNA expression and clinical information of patients with oligodendroglioma were taken from the TCGA "Brain Lower Grade Glioma" provisional dataset. Transcription factor network reconstruction and analysis were performed using the R packages "RTN" and "RTNsurvival." Elastic net regularization and survival modeling were performed using the "biospear," "plsRCox," "survival" packages.

Results: From our cohort of 137 patients, 65 received adjuvant radiation and 72 were observed. In the cohort that received adjuvant radiotherapy, a transcription factor activity signature, that correlated with hypoxia, was associated with shorter disease-free survival (DFS) (median = 45 months vs 108 months, P < .001). This increased risk was not seen in patients who were observed (P = .2). Within the observation cohort, a transcription factor activity signature was generated that was associated with poor DFS (median = 72 months. vs 143 months., P < .01).

Conclusions: We identified a transcription factor activity signature associated with poor prognosis in patients with molecular oligodendroglioma treated with adjuvant radiotherapy. These patients would be potential candidates for treatment intensification. A second signature was generated for patients who were more likely to progress on observation. This potentially identifies a cohort who would benefit from upfront adjuvant radiotherapy.

Keywords: adjuvant radiotherapy; biomarkers; oligodendroglioma.