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Algorithmically deduced FREM2 molecular pathway is a potent grade and survival biomarker of human gliomas
ID
Zolotovskaia, Marianna
(
Author
),
ID
Zottel, Alja
(
Author
),
ID
Šamec, Neja
(
Author
),
ID
Jovchevska, Ivana
(
Author
), et al.
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MD5: 6C2D8E8EB22781D21EE9D98613C60CD0
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https://www.mdpi.com/2072-6694/13/16/4117
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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.
Language:
English
Keywords:
glioma
,
glioblastoma
,
survival prognosis
,
FREM2
,
algorithmically deduced molecular pathway
,
transcriptomics
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
MF - Faculty of Medicine
Publication status:
Published
Publication version:
Version of Record
Year:
2021
Number of pages:
21 str.
Numbering:
Vol. 13, iss. 16, art. 4117
PID:
20.500.12556/RUL-135973
UDC:
616-006
ISSN on article:
2072-6694
DOI:
10.3390/cancers13164117
COBISS.SI-ID:
73102083
Publication date in RUL:
05.04.2022
Views:
649
Downloads:
97
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Record is a part of a journal
Title:
Cancers
Shortened title:
Cancers
Publisher:
MDPI
ISSN:
2072-6694
COBISS.SI-ID:
517914137
Licences
License:
CC BY 4.0, Creative Commons Attribution 4.0 International
Link:
http://creativecommons.org/licenses/by/4.0/
Description:
This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:
16.08.2021
Secondary language
Language:
Slovenian
Keywords:
gliom
,
glioblastom
,
napoved preživetja
Projects
Funder:
EC - European Commission
Funding programme:
ERA-NET EuroTransBio
Funder:
Other - Other funder or multiple funders
Funding programme:
Federal Ministry of Education and Research (BMBF)
Acronym:
OMICSGLIOMA
Funder:
EC - European Commission
Funding programme:
ERA-NET RUS Plus
Acronym:
GOTICS
Funder:
ARRS - Slovenian Research Agency
Project number:
Z3-1869
Name:
Razvoj anti-FREM2 nanotelesa in njegova uporaba pri ciljanju glioblastomskih celic
Funder:
Other - Other funder or multiple funders
Funding programme:
Russian Foundation for Basic Research
Project number:
20-515-76007
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