Identification of IDH-mutant gliomas by a prognostic signature according to gene expression profiling

Aging (Albany NY). 2018 Aug 15;10(8):1977-1988. doi: 10.18632/aging.101521.

Abstract

Background: Isocitrate dehydrogenase (IDH) mutations are the most common genetic aberrations in gliomagenesis. We aimed to build a high-efficiency prediction gene signature in patients with IDH-mutant glioma.

Methods: In total, 167 gliomas from Chinese Glioma Genome Atlas (CGGA) dataset were included for discovery. The Cancer Genome Atlas (TCGA) dataset was used for validation. R language was the main software environment for our statistical operation and graphics.

Results: We applied the Time-Dependent ROC Curve (timeROC) method to estimate the gene prediction accuracy of 3 years and 5 years in two datasets. Seven genes were selected for further analysis (AUC ≥ 0.7 in two datasets). A seven-gene enrichment score was established to predict the overall survival of 3 years and 5 years for IDH- mutant glioma patients. Moreover, the seven-gene signature was an independent prognostic indicator for patients with IDH-mutant glioma. Gene Ontology (GO) Analysis of associated genes revealed signature-related biological process of cell cycle and division.

Conclusion: We have identified a seven-gene signature that can provide a more accurate predictor of 3 years and 5 years for patients with IDH-mutant glioma. Moreover, the signature may potentially help neurosurgeons with the clinical personalized management of gliomas.

Keywords: IDH-mutant gliomas; mRNA; prognostic signature; timeROC.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glioma / enzymology
  • Glioma / genetics*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism*
  • Male
  • Middle Aged
  • Mutation
  • Transcriptome*
  • Young Adult

Substances

  • IDH2 protein, human
  • Isocitrate Dehydrogenase