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Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas

Gliomas are the most commonly occurring malignant brain tumor characterized by an immunosuppressive microenvironment accompanied by profound epigenetic changes, thus influencing the prognosis. Glutathione peroxidase 7 (GPX7) is essential for regulating reactive oxygen species homeostasis under oxida...

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Autores principales: Ferreira, Wallax Augusto Silva, Vitiello, Glauco Akelinghton Freire, da Silva Medina, Tiago, de Oliveira, Edivaldo Herculano Correa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018725/
https://www.ncbi.nlm.nih.gov/pubmed/35440701
http://dx.doi.org/10.1038/s41598-022-10114-1
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author Ferreira, Wallax Augusto Silva
Vitiello, Glauco Akelinghton Freire
da Silva Medina, Tiago
de Oliveira, Edivaldo Herculano Correa
author_facet Ferreira, Wallax Augusto Silva
Vitiello, Glauco Akelinghton Freire
da Silva Medina, Tiago
de Oliveira, Edivaldo Herculano Correa
author_sort Ferreira, Wallax Augusto Silva
collection PubMed
description Gliomas are the most commonly occurring malignant brain tumor characterized by an immunosuppressive microenvironment accompanied by profound epigenetic changes, thus influencing the prognosis. Glutathione peroxidase 7 (GPX7) is essential for regulating reactive oxygen species homeostasis under oxidative stress. However, little is known about the function of GPX7 in gliomas. In this study, we hypothesized that GPX7 methylation status could influence biological functions and local immune responses that ultimately impact prognosis in adult gliomas. We conducted an integrated bioinformatics analysis mining GPX7 DNA methylation status, transcriptional and survival data of glioma patients. We discovered that GPX7 was remarkably increased in glioma tissues and cell lines, and was associated with poor prognosis. This upregulation was significantly linked to clinicopathological and molecular features, besides being expressed in a cell cycle-dependent manner. Our results consistently demonstrated that upregulation of GPX7 is tightly modulated by epigenetic processes, which also impacted the overall survival of patients with low-grade gliomas (LGG). Based on the analysis of biological functions, we found that GPX7 might be involved in immune mechanisms involving both innate and adaptive immunity, type I interferon production and regulation of synaptic transmission in LGG, whereas in GBM, it is mainly related to metabolic regulation of mitochondrial dynamics. We also found that GPX7 strongly correlates with immune cell infiltration and diverse immune cell markers, suggesting its role in tumor-specific immune response and in regulating the migration of immune cell types to the tumor microenvironment. Combining these multiple data, we provided the first evidence regarding the epigenetic-mediated regulatory mechanisms underlying GPX7 activation in gliomas. Furthermore, our study brings key insights into the significant effect of GPX7 in modulating both immune molecules and in immune cell infiltration in the microenvironment of gliomas, which might impact the patient outcome, opening up future opportunities to regulate the local immune response.
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spelling pubmed-90187252022-04-21 Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas Ferreira, Wallax Augusto Silva Vitiello, Glauco Akelinghton Freire da Silva Medina, Tiago de Oliveira, Edivaldo Herculano Correa Sci Rep Article Gliomas are the most commonly occurring malignant brain tumor characterized by an immunosuppressive microenvironment accompanied by profound epigenetic changes, thus influencing the prognosis. Glutathione peroxidase 7 (GPX7) is essential for regulating reactive oxygen species homeostasis under oxidative stress. However, little is known about the function of GPX7 in gliomas. In this study, we hypothesized that GPX7 methylation status could influence biological functions and local immune responses that ultimately impact prognosis in adult gliomas. We conducted an integrated bioinformatics analysis mining GPX7 DNA methylation status, transcriptional and survival data of glioma patients. We discovered that GPX7 was remarkably increased in glioma tissues and cell lines, and was associated with poor prognosis. This upregulation was significantly linked to clinicopathological and molecular features, besides being expressed in a cell cycle-dependent manner. Our results consistently demonstrated that upregulation of GPX7 is tightly modulated by epigenetic processes, which also impacted the overall survival of patients with low-grade gliomas (LGG). Based on the analysis of biological functions, we found that GPX7 might be involved in immune mechanisms involving both innate and adaptive immunity, type I interferon production and regulation of synaptic transmission in LGG, whereas in GBM, it is mainly related to metabolic regulation of mitochondrial dynamics. We also found that GPX7 strongly correlates with immune cell infiltration and diverse immune cell markers, suggesting its role in tumor-specific immune response and in regulating the migration of immune cell types to the tumor microenvironment. Combining these multiple data, we provided the first evidence regarding the epigenetic-mediated regulatory mechanisms underlying GPX7 activation in gliomas. Furthermore, our study brings key insights into the significant effect of GPX7 in modulating both immune molecules and in immune cell infiltration in the microenvironment of gliomas, which might impact the patient outcome, opening up future opportunities to regulate the local immune response. Nature Publishing Group UK 2022-04-19 /pmc/articles/PMC9018725/ /pubmed/35440701 http://dx.doi.org/10.1038/s41598-022-10114-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ferreira, Wallax Augusto Silva
Vitiello, Glauco Akelinghton Freire
da Silva Medina, Tiago
de Oliveira, Edivaldo Herculano Correa
Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas
title Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas
title_full Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas
title_fullStr Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas
title_full_unstemmed Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas
title_short Comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of GPX7 in adult gliomas
title_sort comprehensive analysis of epigenetics regulation, prognostic and the correlation with immune infiltrates of gpx7 in adult gliomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018725/
https://www.ncbi.nlm.nih.gov/pubmed/35440701
http://dx.doi.org/10.1038/s41598-022-10114-1
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