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Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma
INTRODUCTION: Diffuse gliomas have local and global effects on neurophysiological brain functioning, which are often seen as ‘passive’ consequences of the tumor. However, seminal preclinical work has shown a prominent role for neuronal activity in glioma growth: mediated by neuroligin-3 (NLGN3), inc...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244774/ https://www.ncbi.nlm.nih.gov/pubmed/30094719 http://dx.doi.org/10.1007/s11060-018-2967-5 |
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author | Derks, Jolanda Wesseling, Pieter Carbo, Ellen W. S. Hillebrand, Arjan van Dellen, Edwin de Witt Hamer, Philip C. Klein, Martin Schenk, Geert J. Geurts, Jeroen J. G. Reijneveld, Jaap C. Douw, Linda |
author_facet | Derks, Jolanda Wesseling, Pieter Carbo, Ellen W. S. Hillebrand, Arjan van Dellen, Edwin de Witt Hamer, Philip C. Klein, Martin Schenk, Geert J. Geurts, Jeroen J. G. Reijneveld, Jaap C. Douw, Linda |
author_sort | Derks, Jolanda |
collection | PubMed |
description | INTRODUCTION: Diffuse gliomas have local and global effects on neurophysiological brain functioning, which are often seen as ‘passive’ consequences of the tumor. However, seminal preclinical work has shown a prominent role for neuronal activity in glioma growth: mediated by neuroligin-3 (NLGN3), increased neuronal activity causes faster glioma growth. It is unclear whether the same holds true in patients. Here, we investigate whether lower levels of oscillatory brain activity relate to lower NLGN3 expression and predict longer progression free survival (PFS) in diffuse glioma patients. METHODS: Twenty-four newly diagnosed patients with diffuse glioma underwent magnetoencephalography and subsequent tumor resection. Oscillatory brain activity was approximated by calculating broadband power (0.5–48 Hz) of the magnetoencephalography. NLGN3 expression in glioma tissue was semi-quantitatively assessed by immunohistochemistry. Peritumor and global oscillatory brain activity was then compared between different levels of NLGN3 expression with Kruskal–Wallis tests. Cox proportional hazards analyses were performed to estimate the predictive value of oscillatory brain activity for PFS. RESULTS: Patients with low expression of NLGN3 had lower levels of global oscillatory brain activity than patients with higher NLGN3 expression (P < 0.001). Moreover, lower peritumor (hazard ratio 2.17, P = 0.008) and global oscillatory brain activity (hazard ratio 2.10, P = 0.008) predicted longer PFS. CONCLUSIONS: Lower levels of peritumor and global oscillatory brain activity are related to lower NLGN3 expression and longer PFS, corroborating preclinical research. This study highlights the important interplay between macroscopically measured brain activity and glioma progression, and may lead to new therapeutic interventions in diffuse glioma patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11060-018-2967-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6244774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-62447742018-12-04 Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma Derks, Jolanda Wesseling, Pieter Carbo, Ellen W. S. Hillebrand, Arjan van Dellen, Edwin de Witt Hamer, Philip C. Klein, Martin Schenk, Geert J. Geurts, Jeroen J. G. Reijneveld, Jaap C. Douw, Linda J Neurooncol Clinical Study INTRODUCTION: Diffuse gliomas have local and global effects on neurophysiological brain functioning, which are often seen as ‘passive’ consequences of the tumor. However, seminal preclinical work has shown a prominent role for neuronal activity in glioma growth: mediated by neuroligin-3 (NLGN3), increased neuronal activity causes faster glioma growth. It is unclear whether the same holds true in patients. Here, we investigate whether lower levels of oscillatory brain activity relate to lower NLGN3 expression and predict longer progression free survival (PFS) in diffuse glioma patients. METHODS: Twenty-four newly diagnosed patients with diffuse glioma underwent magnetoencephalography and subsequent tumor resection. Oscillatory brain activity was approximated by calculating broadband power (0.5–48 Hz) of the magnetoencephalography. NLGN3 expression in glioma tissue was semi-quantitatively assessed by immunohistochemistry. Peritumor and global oscillatory brain activity was then compared between different levels of NLGN3 expression with Kruskal–Wallis tests. Cox proportional hazards analyses were performed to estimate the predictive value of oscillatory brain activity for PFS. RESULTS: Patients with low expression of NLGN3 had lower levels of global oscillatory brain activity than patients with higher NLGN3 expression (P < 0.001). Moreover, lower peritumor (hazard ratio 2.17, P = 0.008) and global oscillatory brain activity (hazard ratio 2.10, P = 0.008) predicted longer PFS. CONCLUSIONS: Lower levels of peritumor and global oscillatory brain activity are related to lower NLGN3 expression and longer PFS, corroborating preclinical research. This study highlights the important interplay between macroscopically measured brain activity and glioma progression, and may lead to new therapeutic interventions in diffuse glioma patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11060-018-2967-5) contains supplementary material, which is available to authorized users. Springer US 2018-08-09 2018 /pmc/articles/PMC6244774/ /pubmed/30094719 http://dx.doi.org/10.1007/s11060-018-2967-5 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Clinical Study Derks, Jolanda Wesseling, Pieter Carbo, Ellen W. S. Hillebrand, Arjan van Dellen, Edwin de Witt Hamer, Philip C. Klein, Martin Schenk, Geert J. Geurts, Jeroen J. G. Reijneveld, Jaap C. Douw, Linda Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma |
title | Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma |
title_full | Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma |
title_fullStr | Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma |
title_full_unstemmed | Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma |
title_short | Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma |
title_sort | oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244774/ https://www.ncbi.nlm.nih.gov/pubmed/30094719 http://dx.doi.org/10.1007/s11060-018-2967-5 |
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