Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms.
Despite advances in surgical and adjuvant treatments, overall survival of glioblastoma (GBM) patients remains poor. The cancer stem cell concept suggests that a rare stem cell population, called glioma stem cells (GSCs), has high ability to self-renewal leading to recurrence in GBM. The identification of specific markers of GSCs would provide a powerful tool to detect and to characterise them in order to develop targeted therapies. We carried out a comparative analysis based on the identification of inter-study concordances to identify the genes that exhibit at best differential levels of expression between GSC-enriched cell cultures and differentiated tumour cell cultures from independent studies using DNA chip microarray technologies. We finally studied the protein expression of the marker we considered the most specific by immunohistochemistry and semi-quantitative analysis on a retrospective series of 18 GBMs. Of the selected studies, 32 genes were retained. Among them, eight genes were identified to be overexpressed in GSC-enriched cultures compared to differentiated tumour cell cultures. Finally, among the eight genes, oligodendrocyte lineage transcription factor 2 (OLIG2) was characterised by the most different expression level in the "GSC model" compared to the "differentiated tumour cells model". Our approach suggests that OLIG2 is the most specific GSC marker; additional investigations with careful considerations about methodology and strategies of validation are, however, mandatory.
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
Anne-Laure
AL
Trépant
Christelle
C
Bouchart
Sandrine
S
Rorive
Sébastien
S
Sauvage
Christine
C
Decaestecker
Pieter
P
Demetter
Isabelle
I
Salmon
D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012189:Retrospective Studies; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D014157:Transcription Factors; C405708:OLIG2 protein, human