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High FREM2 Gene and Protein Expression Are Associated with Favorable Prognosis of IDH-WT Glioblastomas

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...

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Autores principales: Jovčevska, Ivana, Zottel, Alja, Šamec, Neja, Mlakar, Jernej, Sorokin, Maxim, Nikitin, Daniil, Buzdin, Anton A., Komel, Radovan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721429/
https://www.ncbi.nlm.nih.gov/pubmed/31357584
http://dx.doi.org/10.3390/cancers11081060
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author Jovčevska, Ivana
Zottel, Alja
Šamec, Neja
Mlakar, Jernej
Sorokin, Maxim
Nikitin, Daniil
Buzdin, Anton A.
Komel, Radovan
author_facet Jovčevska, Ivana
Zottel, Alja
Šamec, Neja
Mlakar, Jernej
Sorokin, Maxim
Nikitin, Daniil
Buzdin, Anton A.
Komel, Radovan
author_sort Jovčevska, Ivana
collection PubMed
description 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.
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spelling pubmed-67214292019-09-10 High FREM2 Gene and Protein Expression Are Associated with Favorable Prognosis of IDH-WT Glioblastomas Jovčevska, Ivana Zottel, Alja Šamec, Neja Mlakar, Jernej Sorokin, Maxim Nikitin, Daniil Buzdin, Anton A. Komel, Radovan Cancers (Basel) Article 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. MDPI 2019-07-27 /pmc/articles/PMC6721429/ /pubmed/31357584 http://dx.doi.org/10.3390/cancers11081060 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jovčevska, Ivana
Zottel, Alja
Šamec, Neja
Mlakar, Jernej
Sorokin, Maxim
Nikitin, Daniil
Buzdin, Anton A.
Komel, Radovan
High FREM2 Gene and Protein Expression Are Associated with Favorable Prognosis of IDH-WT Glioblastomas
title High FREM2 Gene and Protein Expression Are Associated with Favorable Prognosis of IDH-WT Glioblastomas
title_full High FREM2 Gene and Protein Expression Are Associated with Favorable Prognosis of IDH-WT Glioblastomas
title_fullStr High FREM2 Gene and Protein Expression Are Associated with Favorable Prognosis of IDH-WT Glioblastomas
title_full_unstemmed High FREM2 Gene and Protein Expression Are Associated with Favorable Prognosis of IDH-WT Glioblastomas
title_short High FREM2 Gene and Protein Expression Are Associated with Favorable Prognosis of IDH-WT Glioblastomas
title_sort high frem2 gene and protein expression are associated with favorable prognosis of idh-wt glioblastomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721429/
https://www.ncbi.nlm.nih.gov/pubmed/31357584
http://dx.doi.org/10.3390/cancers11081060
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