Mesenchymal and Proneural Subtypes of Glioblastoma Disclose Branching Based on GSC Associated Signature

Int J Mol Sci. 2021 May 7;22(9):4964. doi: 10.3390/ijms22094964.

Abstract

Glioblastomas (GBM)-the most common, therapy-resistant, and lethal tumors driven by populations of glioma stem cells (GSCs) are still on the list of the most complicated pathologies. Thus, deeper understanding and characterization of GSCs is indispensable to find suitable targets and develop more effective therapies. In the present study, we applied native glioblastoma cells and GSCs sequencing, screened for GSC-specific targets and checked if the signature is related to GBM patient pathological, clinical data as well as molecular subtypes applying TCGA cohort. Data analysis revealed that tumors of proneural and mesenchymal subtypes are branching in separate clusters based on screened gene expression. Samples of the same subtype revealed significantly different patient survival prognosis as well as recurrence chance between the clusters. Recently, different subpopulations of mesenchymal GSC demonstrating different properties were shown, which indicates possible internal heterogeneity of GBM subtypes as well. Current findings also revealed branching of molecular GBM subtypes that were significantly linked to patient outcome and that might be decided by distinct GSC subpopulations.

Keywords: biomarkers; glioblastoma; glioma stem cells; mesenchymal; proneural; subtyping.

MeSH terms

  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cluster Analysis
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mesoderm / pathology*
  • Middle Aged
  • Molecular Sequence Annotation
  • Neoplasm Recurrence, Local / pathology
  • Neoplastic Stem Cells / metabolism*
  • Principal Component Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • RNA, Messenger