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Combined expressional analysis, bioinformatics and targeted proteomics identify new potential therapeutic targets in glioblastoma stem cells

Stangeland, Biljana
Mughal, Awais A
Grieg, Zanina
Sandberg, Cecilie Jonsgar
Joel, Mrinal
Nygård, Ståle
Murrell, Wayne
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Published in Oncotarget. 2015, vol. 6, no. 28, p. 26192-215
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.
Keywords AnimalsAntineoplastic Agents/therapeutic useBiomarkersTumor/genetics/metabolismBrain Neoplasms/drug therapy/genetics/metabolism/mortality/pathologyCell DifferentiationCell LineTumorCell ProliferationComputational BiologyDrug DesignGene Expression Profiling/methodsGene Expression RegulationNeoplasticGenotypeGlioblastoma/drug therapy/genetics/metabolism/mortality/pathologyHeterograftsHumansMiceMolecular Targeted TherapyNeoplasm TransplantationNeoplastic Stem Cells/drug effects/metabolism/pathologyNeural Stem Cells/drug effects/metabolism/pathologyOligonucleotide Array Sequence AnalysisPhenotypePrognosisProtein Interaction MapsProteomics/methodsSignal TransductionSurvival AnalysisTime FactorsTumor CellsCultured
PMID: 26295306
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Research group Groupe Schaller Karl Lothard (neurochirurgie) (851)
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STANGELAND, Biljana et al. Combined expressional analysis, bioinformatics and targeted proteomics identify new potential therapeutic targets in glioblastoma stem cells. In: Oncotarget, 2015, vol. 6, n° 28, p. 26192-215. doi: 10.18632/oncotarget.4613 https://archive-ouverte.unige.ch/unige:111892

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Deposited on : 2018-12-05

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