High FREM2 gene and protein expression are associated with favorable prognosis of IDH-WT glioblastomas

Jovchevska, Ivana (avtor), Zottel, Alja (avtor), Šamec, Neja (avtor), Mlakar, Jernej (avtor), Sorokin, Maxim (avtor), Nikitin, Daniil (avtor), Buzdin, Anton A. (avtor), Komel, Radovan (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: glioblastoma, malignancy, FREM2, SPRY1, TCGA
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2019
• Št. strani: 18 str.
• Številčenje: Vol. 11, iss. 8, art. 1060
• PID: 20.500.12556/RUL-128755
• UDK: 616-006
• ISSN pri članku: 2072-6694
• DOI: 10.3390/cancers11081060
• COBISS.SI-ID: 34433753
• Datum objave v RUL: 27.07.2021

Gradivo je del revije

• Naslov: Cancers
• Skrajšan naslov: Cancers
• Založnik: MDPI
• ISSN: 2072-6694
• COBISS.SI-ID: 517914137

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.08.2019

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: glioblastom, malignost