Algorithmically Deduced <i>FREM2</i> Molecular Pathway Is a Potent Grade and Survival Biomarker of Human Gliomas
Gliomas are the most common malignant brain tumors with high mortality rates. Recently we showed that the <i>FREM2</i> gene has a role in glioblastoma progression. Here we reconstructed the <i>FREM2</i> molecular pathway using the human interactome model. We assessed the biom...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/16/4117 |
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| author | Marianna Zolotovskaia Victor Tkachev Maxim Sorokin Andrew Garazha Ella Kim Sven Rainer Kantelhardt Sven-Ernö Bikar Alja Zottel Neja Šamec Denis Kuzmin Bettina Sprang Alexey Moisseev Alf Giese Victor Efimov Ivana Jovčevska Anton Buzdin |
| author_facet | Marianna Zolotovskaia Victor Tkachev Maxim Sorokin Andrew Garazha Ella Kim Sven Rainer Kantelhardt Sven-Ernö Bikar Alja Zottel Neja Šamec Denis Kuzmin Bettina Sprang Alexey Moisseev Alf Giese Victor Efimov Ivana Jovčevska Anton Buzdin |
| author_sort | Marianna Zolotovskaia |
| collection | DOAJ |
| description | Gliomas are the most common malignant brain tumors with high mortality rates. Recently we showed that the <i>FREM2</i> gene has a role in glioblastoma progression. Here we reconstructed the <i>FREM2</i> molecular pathway using the human interactome model. We assessed the biomarker capacity of <i>FREM2</i> 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 <i>FREM2</i> pathway showed strong biomarker characteristics and significantly outperformed the <i>FREM2</i> expression level itself. For all relevant datasets, it could robustly discriminate GBM and LGG (<i>p</i> < 1.63 × 10<sup>−13</sup>, AUC > 0.74). High <i>FREM2</i> pathway activation level was associated with poor OS in LGG (<i>p</i> < 0.001), and low PFS in LGG (<i>p</i> < 0.001) and GBM (<i>p</i> < 0.05). <i>FREM2</i> pathway activation level was poor prognosis biomarker for OS (<i>p</i> < 0.05) and PFS (<i>p</i> < 0.05) in LGG with <i>IDH</i> mutation, for PFS in LGG with wild type <i>IDH</i> (<i>p</i> < 0.001) and mutant <i>IDH</i> with 1p/19q codeletion(<i>p</i> < 0.05), in GBM with unmethylated <i>MGMT</i> (<i>p</i> < 0.05), and in GBM with wild type <i>IDH</i> (<i>p</i> < 0.05). Thus, we conclude that the activation level of the <i>FREM2</i> pathway is a potent new-generation diagnostic and prognostic biomarker for multiple molecular subtypes of GBM and LGG. |
| first_indexed | 2024-03-10T08:56:20Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:56:20Z |
| publishDate | 2021-08-01 |
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| series | Cancers |
| spelling | doaj.art-3acaa5776f0c4b5a94c73cecbb3f5fa52023-11-22T07:04:02ZengMDPI AGCancers2072-66942021-08-011316411710.3390/cancers13164117Algorithmically Deduced <i>FREM2</i> Molecular Pathway Is a Potent Grade and Survival Biomarker of Human GliomasMarianna Zolotovskaia0Victor Tkachev1Maxim Sorokin2Andrew Garazha3Ella Kim4Sven Rainer Kantelhardt5Sven-Ernö Bikar6Alja Zottel7Neja Šamec8Denis Kuzmin9Bettina Sprang10Alexey Moisseev11Alf Giese12Victor Efimov13Ivana Jovčevska14Anton Buzdin15Omicsway Corp., Walnut, CA 91789, USAMoscow Institute of Physics and Technology, Dolgoprudny 141701, RussiaOmicsway Corp., Walnut, CA 91789, USAOmicsway Corp., Walnut, CA 91789, USAClinic for Neurosurgery, Laboratory of Experimental Neurooncology, Johannes Gutenberg University Medical Centre, Langenbeckstrasse 1, 55124 Mainz, GermanyClinic for Neurosurgery, Laboratory of Experimental Neurooncology, Johannes Gutenberg University Medical Centre, Langenbeckstrasse 1, 55124 Mainz, GermanyStarSEQ GmbH, Joh.-Joachim-Becher-Weg 30a, 55128 Mainz, GermanyMedical Center for Molecular Biology, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000 Ljubljana, SloveniaMedical Center for Molecular Biology, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000 Ljubljana, SloveniaMoscow Institute of Physics and Technology, Dolgoprudny 141701, RussiaClinic for Neurosurgery, Laboratory of Experimental Neurooncology, Johannes Gutenberg University Medical Centre, Langenbeckstrasse 1, 55124 Mainz, GermanyOmicsway Corp., Walnut, CA 91789, USAOrthocentrum Hamburg, Hansastrasse 1, 20149 Hamburg, GermanyMoscow Institute of Physics and Technology, Dolgoprudny 141701, RussiaMedical Center for Molecular Biology, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000 Ljubljana, SloveniaMoscow Institute of Physics and Technology, Dolgoprudny 141701, RussiaGliomas are the most common malignant brain tumors with high mortality rates. Recently we showed that the <i>FREM2</i> gene has a role in glioblastoma progression. Here we reconstructed the <i>FREM2</i> molecular pathway using the human interactome model. We assessed the biomarker capacity of <i>FREM2</i> 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 <i>FREM2</i> pathway showed strong biomarker characteristics and significantly outperformed the <i>FREM2</i> expression level itself. For all relevant datasets, it could robustly discriminate GBM and LGG (<i>p</i> < 1.63 × 10<sup>−13</sup>, AUC > 0.74). High <i>FREM2</i> pathway activation level was associated with poor OS in LGG (<i>p</i> < 0.001), and low PFS in LGG (<i>p</i> < 0.001) and GBM (<i>p</i> < 0.05). <i>FREM2</i> pathway activation level was poor prognosis biomarker for OS (<i>p</i> < 0.05) and PFS (<i>p</i> < 0.05) in LGG with <i>IDH</i> mutation, for PFS in LGG with wild type <i>IDH</i> (<i>p</i> < 0.001) and mutant <i>IDH</i> with 1p/19q codeletion(<i>p</i> < 0.05), in GBM with unmethylated <i>MGMT</i> (<i>p</i> < 0.05), and in GBM with wild type <i>IDH</i> (<i>p</i> < 0.05). Thus, we conclude that the activation level of the <i>FREM2</i> pathway is a potent new-generation diagnostic and prognostic biomarker for multiple molecular subtypes of GBM and LGG.https://www.mdpi.com/2072-6694/13/16/4117<i>FREM2</i>gliomaglioblastomasurvival prognosisalgorithmically deduced molecular pathwaytranscriptomics |
| spellingShingle | Marianna Zolotovskaia Victor Tkachev Maxim Sorokin Andrew Garazha Ella Kim Sven Rainer Kantelhardt Sven-Ernö Bikar Alja Zottel Neja Šamec Denis Kuzmin Bettina Sprang Alexey Moisseev Alf Giese Victor Efimov Ivana Jovčevska Anton Buzdin Algorithmically Deduced <i>FREM2</i> Molecular Pathway Is a Potent Grade and Survival Biomarker of Human Gliomas Cancers <i>FREM2</i> glioma glioblastoma survival prognosis algorithmically deduced molecular pathway transcriptomics |
| title | Algorithmically Deduced <i>FREM2</i> Molecular Pathway Is a Potent Grade and Survival Biomarker of Human Gliomas |
| title_full | Algorithmically Deduced <i>FREM2</i> Molecular Pathway Is a Potent Grade and Survival Biomarker of Human Gliomas |
| title_fullStr | Algorithmically Deduced <i>FREM2</i> Molecular Pathway Is a Potent Grade and Survival Biomarker of Human Gliomas |
| title_full_unstemmed | Algorithmically Deduced <i>FREM2</i> Molecular Pathway Is a Potent Grade and Survival Biomarker of Human Gliomas |
| title_short | Algorithmically Deduced <i>FREM2</i> Molecular Pathway Is a Potent Grade and Survival Biomarker of Human Gliomas |
| title_sort | algorithmically deduced i frem2 i molecular pathway is a potent grade and survival biomarker of human gliomas |
| topic | <i>FREM2</i> glioma glioblastoma survival prognosis algorithmically deduced molecular pathway transcriptomics |
| url | https://www.mdpi.com/2072-6694/13/16/4117 |
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