Profiling Glioblastoma Cases with an Expression of DCX, OLIG2 and NES

Int J Mol Sci. 2021 Dec 8;22(24):13217. doi: 10.3390/ijms222413217.

Abstract

Glioblastoma (GBM) remains the leading cause of cancer-related deaths with the lowest five-year survival rates among all of the human cancers. Multiple factors contribute to its poor outcome, including intratumor heterogeneity, along with migratory and invasive capacities of tumour cells. Over the last several years Doublecortin (DCX) has been one of the debatable factors influencing GBM cells' migration. To resolve DCX's ambiguous role in GBM cells' migration, we set to analyse the expression patterns of DCX along with Nestin (NES) and Oligodendrocyte lineage transcription factor 2 (OLIG2) in 17 cases of GBM, using immunohistochemistry, followed by an analysis of single-cell RNA-seq data. Our results showed that only a small subset of DCX positive (DCX+) cells was present in the tumour. Moreover, no particular pattern emerged when analysing DCX+ cells relative position to the tumour margin. By looking into single-cell RNA-seq data, the majority of DCX+ cells were classified as non-cancerous, with a small subset of cells that could be regarded as glioma stem cells. In conclusion, our findings support the notion that glioma cells express DCX; however, there is no clear evidence to prove that DCX participates in GBM cell migration.

Keywords: DCX; Doublecortin; Glioblastoma; NES; OLIG2; brain tumours; immunofluorescence; immunohistochemistry; single cell RNA-seq.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Cell Movement
  • Doublecortin Protein / genetics
  • Doublecortin Protein / metabolism*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Heuristics
  • Humans
  • Image Processing, Computer-Assisted
  • Microscopy, Confocal
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / metabolism
  • Nestin / genetics
  • Nestin / metabolism*
  • Oligodendrocyte Transcription Factor 2 / genetics
  • Oligodendrocyte Transcription Factor 2 / metabolism*
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Survival Analysis

Substances

  • DCX protein, human
  • Doublecortin Protein
  • NES protein, human
  • Nestin
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2