20.500.12556/RUL-131851 Meta-analysis and experimental validation identified FREM2 and SPRY1 as new glioblastoma marker candidates 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. glioblastoma glioblastoma stem cells biomarkers data repositories meta-analysis cell surface experimental validation FREM2 SPRY1 glioblastom matične celice glioblastoma biomarkerji true false true Angleški jezik Slovenski jezik Članek v reviji 2021-10-04 14:52:35 2021-10-04 14:52:38 2022-09-10 04:14:10 0000-00-00 00:00:00 2018 0 0 24 str. iss. 5, art. 1369 Vol. 19 May 2018 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577 1422-0067 10.3390/ijms19051369 33752793 RAZ_Vidak_Marko_2018.pdf RAZ_Vidak_Marko_2018.pdf 1 83FE430F48BFB92CCC15C1E10F308C74 bc1dcbb589eb7c07bf98307c2bdbb7a7b695b56aa0796799ec48af4a9550e53a 15a00146-2512-11ec-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=149271 http://www.mdpi.com/1422-0067/19/5/1369 1 aa4dafd3-2511-11ec-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=149270 Medicinska fakulteta 0 0 0