Elevated E2F7 expression predicts poor prognosis in human patients with gliomas

J Clin Neurosci. 2016 Nov:33:187-193. doi: 10.1016/j.jocn.2016.04.019. Epub 2016 Jul 22.

Abstract

E2F transcription factors have been studied extensively in a broad range of organisms as major regulators of cell cycle, apoptosis, and differentiation. The E2F family includes the atypical member E2F7, which has been rarely studied in gliomas. The aim of this study is to determine the expression status of E2F7 in gliomas, its relationship to clinicopathological features, and patients' outcome. The mRNA levels of E2F7 in the human brain and different grades of gliomas were analysed using datasets from the publically available Oncomine database. One of the most significant co-expression factors, CDK1, together with E2F7, was further validated by immunohistochemistry in 90 different grades of gliomas. Furthermore, univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumour characteristics and treatment modalities. E2F7 mRNA expression was found to be elevated in gliomas by Oncomine-database analysis. Immunohistochemistry showed an increase in E2F7 labelling index in high- versus low-grade gliomas (62.1±11.8% vs. 18.9±10.2%, p<0.0001). There was a positive correlation between E2F7 and CDK1 immunoreactivity (Spearman r=0.446, p=0.037). Clinicopathological evaluation suggested that E2F7 expression was associated with tumour grade (p<0.0001) and recurrence (p=0.025). In Cox multivariate analysis, pathological classification and recurrence were independent prognostic factors of gliomas, and E2F7 was significantly related to progression-free survival (p=0.011), but not overall survival (p=0.062). Our findings suggested that E2F7 might act as an independent prognostic factor of gliomas and might constitute a potential therapeutic target for this disease.

Keywords: CDK1; E2F7; Glioma; Prognosis; Tumor grade.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics*
  • CDC2 Protein Kinase / biosynthesis
  • CDC2 Protein Kinase / genetics
  • Databases, Factual
  • Disease-Free Survival
  • E2F7 Transcription Factor / biosynthesis*
  • E2F7 Transcription Factor / genetics
  • Female
  • Glioma / diagnosis*
  • Glioma / genetics*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local
  • Predictive Value of Tests
  • Prognosis
  • Survival Analysis

Substances

  • E2F7 Transcription Factor
  • CDC2 Protein Kinase