Marko Vidak (Author), Ivana Jovchevska (Author), Neja Zupanec (Author), Alja Zottel (Author), Mirjana Liović (Author), Damjana Rozman (Author), Sašo Džeroski (Author), Peter Juvan (Author), Radovan Komel (Author)

Abstract

Glioblastoma (GB) is the most aggressive brain malignancy. Although some potential glioblastoma biomarkers have already been identified, there is a lack of cell membrane-bound biomarkers capable of distinguishing brain tissue from glioblastoma and/or glioblastoma stem cells (GSC), which are responsible for the rapid post-operative tumor reoccurrence. In order to find new GB/GSC marker candidates that would be cell surface proteins (CSP), we have performed meta-analysis of genome-scale mRNA expression data from three data repositories (GEO, ArrayExpress and GLIOMASdb). The search yielded ten appropriate datasets, and three (GSE4290/GDS1962, GSE23806/GDS3885, and GLIOMASdb) were used for selection of new GB/GSC marker candidates, while the other seven (GSE4412/GDS1975, GSE4412/GDS1976, E-GEOD-52009, E-GEOD-68848, E-GEOD-16011, E-GEOD-4536, and E-GEOD-74571) were used for bioinformatic validation. The selection identified four new CSP-encoding candidate genes-CD276, FREM2, SPRY1, and SLC47A1-and the bioinformatic validation confirmed these findings. A review of the literature revealed that CD276 is not a novel candidate, while SLC47A1 had lower validation test scores than the other new candidates and was therefore not considered for experimental validation. This validation revealed that the expression of FREM2-but not SPRY1-is higher in glioblastoma cell lines when compared to non-malignant astrocytes. In addition, FREM2 gene and protein expression levels are higher in GB stem-like cell lines than in conventional glioblastoma cell lines. FREM2 is thus proposed as a novel GB biomarker and a putative biomarker of glioblastoma stem cells. Both FREM2 and SPRY1 are expressed on the surface of the GB cells, while SPRY1 alone was found overexpressed in the cytosol of non-malignant astrocytes.

Keywords

glioblastom;23/5000 matične celice glioblastoma;biomarkerji;glioblastoma;glioblastoma stem cells;biomarkers;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 577
COBISS: 33752793 Link will open in a new window
ISSN: 1422-0067
Views: 249
Downloads: 71
Average score: 0 (0 votes)
Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: glioblastom;matične celice glioblastoma;biomarkerji;
Type (COBISS): Article
Pages: str. 1-24
Volume: ǂVol. ǂ19
Issue: ǂiss. ǂ5
Chronology: May 2018
DOI: 10.3390/ijms19051369
ID: 13641432