Marianna Zolotovskaia (Author), Victor Tkachev (Author), Maxim Sorokin (Author), Andrew Garazha (Author), Ella Kim (Author), Sven Rainer Kantelhardt (Author), Alja Zottel (Author), Neja Zupanec (Author), Ivana Jovchevska (Author)

Abstract

Gliomas are the most common malignant brain tumors with high mortality rates. Recently we showed that the FREM2 gene has a role in glioblastoma progression. Here we reconstructed the FREM2 molecular pathway using the human interactome model. We assessed the biomarker capacity of FREM2 expression and its pathway as the overall survival (OS) and progression-free survival (PFS) biomarkers. To this end, we used three literature and one experimental RNA sequencing datasets collectively covering 566 glioblastomas (GBM) and 1097 low-grade gliomas (LGG). The activation level of deduced FREM2 pathway showed strong biomarker characteristics and significantly outperformed the FREM2 expression level itself. For all relevant datasets, it could robustly discriminate GBM and LGG (p < 1.63 % 10%13, AUC > 0.74). High FREM2 pathway activation level was associated with poor OS in LGG (p < 0.001), and low PFS in LGG (p < 0.001) and GBM (p < 0.05). FREM2 pathway activation level was poor prognosis biomarker for OS (p < 0.05) and PFS (p < 0.05) in LGG with IDH mutation, for PFS in LGG with wild type IDH (p < 0.001) and mutant IDH with 1p/19q codeletion(p < 0.05), in GBM with unmethylated MGMT (p < 0.05), and in GBM with wild type IDH (p < 0.05). Thus, we conclude that the activation level of the FREM2 pathway is a potent new-generation diagnostic and prognostic biomarker for multiple molecular subtypes of GBM and LGG.

Keywords

gliom;glioblastom;napoved preživetja;glioma;glioblastoma;survival prognosis;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 616-006
COBISS: 73102083 Link will open in a new window
ISSN: 2072-6694
Views: 108
Downloads: 48
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Other data

Secondary language: Slovenian
Secondary keywords: gliom;glioblastom;napoved preživetja;
Type (COBISS): Article
Pages: str. 1-21
Volume: ǂVol. ǂ13
Issue: ǂiss. ǂ16
Chronology: 2021
DOI: 10.3390/cancers13164117
ID: 14947342