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

Adrian Odrzywolski,Dominik Ziemianek,Ilona Telejko,Sebastian Knaga,Radosław Rola,Michał Kiełbus,Bożena Jarosz

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.

Highlights

Even though malignant brain tumours account only for a small percentage of all adult cancers, they lead to an extensive amount of cancer-related deaths [1]
When we look closer at the populations of these cells that had been annotated as ‘normal’, simultaneous expression of Oligodendrocyte lineage transcription factor 2 (OLIG2) and DCX was observed in the clusters of these cells that were expressing markers specific for highly proliferative or undifferentiated cells as well as in the cluster of cells expressing markers that are common for astrocytes, oligodendrocytes and neurons
While Rich et al correlated the mRNA level of DCX with poor diagnosis, Daou et al proved that DCX had more intense staining towards the margin of the tumour using immunostaining

Summary

Introduction

Even though malignant brain tumours account only for a small percentage of all adult cancers, they lead to an extensive amount of cancer-related deaths [1]. The fiveyear survival rates are among the lowest for all human cancers [2], regardless of treatment modality [3]. This remarkable resistance results mostly from tumour heterogeneity and its high propensity for malignant progression. One of the vital pathophysiologic features contributing to this dismal prognosis is their strong migrational capacity [4] for significant dispersal beyond the macroscopic tumour borders [5]. A similar migratory ability is one of the principal features of neuronal progenitor cells (NPC) during CNS development [6,7]. It is worth noticing that data generated by the Cancer

Methods

Results

Conclusion