title: NANOG overexpression and its correlation with stem cell and differentiation markers in meningiomas of different WHO grades.
abstract: NANOG, as a key regulator of pluripotency and acting synergistically with other factors, has been described as a crucial transcription factor in various types of cancer. In meningiomas the expression of this marker has not yet been described. With our study, we aimed to identify and localize NANOG and other possible markers of pluripotency, stem cell properties and differentiation in meningioma tissue, to elucidate a possible effect on tumorigenesis. The gene expression levels of NANOG (NANOG1 and NANOGP8), SOX2, OCT4, KLF4, ABCG2, CMYC, MSI1, CD44, NOTCH1, NES, SALL4B, TP53, and EPAS1 were quantitatively examined using RT-qPCR in 33 surgical specimens of low- (WHO grade I) as well as in high-grade (WHO grade II/III) meningiomas with dural tissue as reference. Immunofluorescence co-localization analysis following confocal fluorescence microscopy for NANOG, OCT4, SOX2, Nestin, KI-67, and CD44 was also performed. There was a significant overexpression of NANOG, MSI1, and EPAS1 and a downregulation of NES in all examined tumors. Subgroup analysis (WHO grade I versus grade II/III) revealed differences in the expression of NANOG, CD44, and MSI1. We found 1% NANOG-positive (NANOG+) cells in low-grade and 2% in grade II/III meningiomas co-expressing the other mentioned markers in various compositions. In particular, NANOG+ cells expressing SOX2 and OCT4 were successfully identified (26% low-grade versus 20% high-grade). Our data reveal an overexpression of NANOG and other markers of pluripotency and stemness in meningiomas. Such potentially pluripotent "stem cell-like" cells may have an impact on tumorigenesis and progression in human meningiomas.
authors.affiliation: Department of Neurosurgery, Section of Experimental Neurooncology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Diana
authors.identifier: 0000-0001-7573-3119
authors.initials: D
authors.lastname: Freitag
authors.affiliation: Department of Neurosurgery, Section of Experimental Neurooncology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Aaron Lawson
authors.initials: AL
authors.lastname: McLean
authors.affiliation: Department of Neurosurgery, Section of Experimental Neurooncology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.|Department of Neurosurgery, Vivantes Klinikum im Friedrichshain, Berlin, Germany.
authors.forename: Michèle
authors.initials: M
authors.lastname: Simon
authors.affiliation: Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Arend
authors.initials: A
authors.lastname: Koch
authors.affiliation: Department of Neurosurgery, Section of Experimental Neurooncology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Grube
authors.affiliation: Department of Neurosurgery, Section of Experimental Neurooncology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Walter
authors.affiliation: Department of Neurosurgery, Section of Experimental Neurooncology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kalff
authors.affiliation: Department of Neurosurgery, Section of Experimental Neurooncology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.|Department of Neurosurgery, Städtisches Klinikum Brandenburg, Brandenburg an der Havel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ewald
mesh_terms: D000943:Antigens, Differentiation / Q000032:analysis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D000071317:Nanog Homeobox Protein / Q000032:analysis / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D000943:Antigens, Differentiation; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein
keywords: NANOG; gene expression; meningioma; pluripotency