Algorithmically deduced FREM2 molecular pathway is a potent grade and survival biomarker of human gliomas
| Autor: | Alf Giese, Victor Tkachev, Andrew Garazha, Anton Buzdin, Alexey Moisseev, Alja Zottel, Ella Kim, Marianna Zolotovskaia, Sven R. Kantelhardt, Denis Kuzmin, Bettina Sprang, Sven-Ernö Bikar, Neja Šamec, Victor Efimov, Ivana Jovčevska, Maxim Sorokin |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Cancer Research
Mutant napoved preživetja Biology Transcriptome transcriptomics Glioma glioma gliom medicine Gene RC254-282 udc:616-006 glioblastom Wild type glioblastoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens survival prognosis Molecular pathway FREM2 medicine.disease nervous system diseases Oncology Cancer research Biomarker (medicine) algorithmically deduced molecular pathway Glioblastoma |
| Zdroj: | Cancers, vol. 13, no. 16, 4117, 2021. Cancers Volume 13 Issue 16 Cancers, Vol 13, Iss 4117, p 4117 (2021) |
| ISSN: | 2072-6694 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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