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

Giedrius Steponaitis,Arimantas Tamasauskas

doi:10.3390/ijms22094964

Giedrius Steponaitis, Arimantas Tamasauskas

Open Access

https://doi.org/10.3390/ijms22094964

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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.

Highlights

Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Citation: Steponaitis, G.; 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
Nanopore sequencing in total resulted in 61,560 sequenced transcripts, of which 38,891 were common between U87-MG and
We screened for glioma stem cells specific gene expression signature by comparing glioblastoma-derived differentiated tumor cells U87-MG and glioblastoma-derived cancer stem cells NCH421K

Summary

Introduction

Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Citation: Steponaitis, G.; 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. 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. Current findings revealed branching of molecular GBM subtypes that were significantly linked to patient outcome and that might be decided by distinct GSC subpopulations. The main feature of glioblastoma (GBM) tumors is their intrinsic resistance to currently applied therapies that leads to extremely poor clinical outcomes and survival that rarely exceeds 15 months after the diagnosis [1]. Substantial evidence has confirmed the existence of glioma initiating/propagating or cancer stem-like cells within

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