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Updated: Apr 5, 2026
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Combined expressional analysis, bioinformatics and targeted proteomics identify new potential therapeutic targets in
Biljana Stangeland1,2, Awais A Mughal1, Zanina Grieg1,3
1Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
Abstract:
Glioblastoma (GBM) is both the most common and the most lethal primary brain tumor. It is thought that GBM stem cells (GSCs) are critically important in resistance to therapy. Therefore, there is a strong rationale to target these cells in order to develop new molecular therapies.To identify molecular targets in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs) from the adult human brain, using microarrays. Bioinformatic filtering identified 20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2, HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC, ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC cultures and consistently not expressed in NSC cultures. The expression of these genes was confirmed in clinical samples (TCGA and REMBRANDT). The first nine genes were highly co-expressed in all GBM subtypes and were part of the same protein-protein interaction network. Furthermore, their combined up-regulation correlated negatively with patient survival in the mesenchymal GBM subtype. Using targeted proteomics and the COGNOSCENTE database we linked these genes to GBM signalling pathways.Nine genes: PBK, CENPA, KIF15, DEPDC1, CDC6, DLG7, KIF18A, EZH2 and HMMR should be further explored as targets for treatment of GBM.
Insights
Researchers identified nine key genes highly expressed in glioblastoma stem cells (GSCs) but not normal neural stem cells (NSCs). These genes represent potential therapeutic targets for glioblastoma, a lethal brain cancer.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genomics
Background:
- Glioblastoma (GBM) is the most common and lethal primary brain tumor.
- Glioblastoma stem cells (GSCs) are implicated in therapeutic resistance.
- Targeting GSCs is a promising strategy for novel GBM therapies.
Purpose of the Study:
- To identify molecular targets specific to GSCs.
- To compare gene expression profiles between GSCs and normal neural stem cells (NSCs).
- To validate potential therapeutic targets in clinical GBM samples.
Main Methods:
- Gene expression profiling using microarrays to compare GSCs and NSCs.
- Bioinformatic analysis to identify differentially expressed genes.
- Validation of gene expression in clinical GBM datasets (TCGA, REMBRANDT) and proteomic analysis.
Main Results:
- Twenty genes consistently expressed in GSCs and not in NSCs were identified.
- Nine genes (PBK, CENPA, KIF15, DEPDC1, CDC6, DLG7, KIF18A, EZH2, HMMR) were highly co-expressed across GBM subtypes.
- Up-regulation of these nine genes correlated with poorer patient survival in the mesenchymal GBM subtype.
Conclusions:
- The identified nine genes are promising molecular targets for GBM treatment.
- These genes are involved in GBM signaling pathways and form a co-expressed network.
- Further exploration of these nine genes is warranted for developing new GBM therapies.
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