Phosphohistone H3 (pHH3) is a prognostic and epithelial to mesenchymal transition marker in diffuse gliomas

Oncotarget. 2016 Jul 19;7(29):45005-45014. doi: 10.18632/oncotarget.7154.

Abstract

The World Health Organization (WHO) grading of gliomas stratifies tumors by histology. However, the aggressiveness of tumors in each grade still shows great heterogeneity. Phosphohistone H3 (pHH3) has been reported as an accurate marker of cells within the mitotic phase of the cell cycle in many kinds of cancers. To evaluate the role of pHH3 in predicting patient outcome and to annotate the functions of pHH3 in WHO grade II-IV gliomas, we analyzed the expression pattern of pHH3 and pHH3 associated genes by IHC and mRNA expression profiling. Phosphohistone H3, mRNA enrichment of histone H3 and associated gene signature all showed prognostic value in adult diffuse gliomas. Gene set enrichment analysis suggested that the expression of pHH3 had positive correlation with both epithelial to mesenchymal transition and immune response. These findings suggest that subgroups of diffuse gliomas defined by pHH3 and pHH3 signatures possess distinctive prognostic and biological characteristics.

Keywords: EMT; glioma; pHH3; prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Profiling
  • Glioma / mortality
  • Glioma / pathology*
  • Histones / analysis
  • Histones / biosynthesis*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Phosphorylation
  • Prognosis
  • Proportional Hazards Models
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • Histones