20.500.12556/RUL-128755 High FREM2 gene and protein expression are associated with favorable prognosis of IDH-WT glioblastomas World Health Organization grade IV diffuse gliomas, known as glioblastomas, are the most common malignant brain tumors, and they show poor prognosis. Multimodal treatment of surgery followed by radiation and chemotherapy is not sufficient to increase patient survival, which is 12 to 18 months after diagnosis. Despite extensive research, patient life expectancy has not significantly improved over the last decade. Previously, we identified FREM2 and SPRY1 as genes with differential expression in glioblastoma cell lines compared to nonmalignant astrocytes. In addition, the FREM2 and SPRY1 proteins show specific localization on the surface of glioblastoma cells. In this study, we explored the roles of the FREM2 and SPRY1 genes and their proteins in glioblastoma pathology using human tissue samples. We used proteomic, transcriptomic, and bioinformatics approaches to detect changes at different molecular levels. We demonstrate increased FREM2 protein expression levels in glioblastomas compared to reference samples. At the transcriptomic level, both FREM2 and SPRY1 show increased expression in tissue samples of different glioma grades compared to nonmalignant brain tissue. To broaden our experimental findings, we analyzed The Cancer Genome Atlas glioblastoma patient datasets. We discovered higher FREM2 and SPRY1 gene expression levels in glioblastomas compared to lower grade gliomas and reference samples. In addition, we observed that low FREM2 expression was associated with progression of IDH-mutant low-grade glioma patients. Multivariate analysis showed positive association between FREM2 and favorable prognosis of IDH-wild type glioblastoma. We conclude that FREM2 has an important role in malignant progression of glioblastoma, and we suggest deeper analysis to determine its involvement in glioblastoma pathology. glioblastoma malignancy FREM2 SPRY1 TCGA glioblastom malignost true false true Angleški jezik Slovenski jezik Članek v reviji 2021-07-27 15:00:27 2021-07-27 15:00:33 2022-09-07 04:16:59 0000-00-00 00:00:00 2019 0 0 18 str. iss. 8, art. 1060 Vol. 11 2019 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006 2072-6694 10.3390/cancers11081060 34433753 RAZ_Jovchevska_Ivana_2019.pdf RAZ_Jovchevska_Ivana_2019.pdf 1 3855776643CD1FAD9F78ADFB6848DC7B dd736e16ef2964d775f3870cd15fb875bffd3c9268fe804506616a2fbfb1904c 77b1b954-eeda-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=145610 https://www.mdpi.com/2072-6694/11/8/1060 0 a3d1b216-eeda-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=145611 Medicinska fakulteta 0 0 0