Abstract

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.

Original languageEnglish
Pages (from-to)403-412
Number of pages10
JournalJournal of Neuro-Oncology
Volume140
Issue number2
DOIs
Publication statusPublished - Nov 2018

Cite this

@article{22f3bbb7d4cf4da886d17084986a1f34,
title = "Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma",
abstract = "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.",
keywords = "Adolescent, Adult, Biomarkers, Tumor/metabolism, Brain/pathology, Brain Neoplasms/diagnosis, Brain Waves/physiology, Cell Adhesion Molecules, Neuronal/metabolism, Cohort Studies, Disease Progression, Female, Gene Expression Regulation, Neoplastic, Glioma/diagnosis, Humans, Magnetoencephalography, Male, Membrane Proteins/metabolism, Middle Aged, Nerve Tissue Proteins/metabolism, Prognosis, Progression-Free Survival",
author = "Jolanda Derks and Pieter Wesseling and Carbo, {Ellen W S} and Arjan Hillebrand and {van Dellen}, Edwin and {de Witt Hamer}, {Philip C} and Martin Klein and Schenk, {Geert J} and Geurts, {Jeroen J G} and Reijneveld, {Jaap C} and Linda Douw",
year = "2018",
month = "11",
doi = "10.1007/s11060-018-2967-5",
language = "English",
volume = "140",
pages = "403--412",
journal = "Journal of Neuro-Oncology",
issn = "0167-594X",
publisher = "Kluwer Academic Publishers",
number = "2",

}

TY - JOUR

T1 - Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma

AU - Derks, Jolanda

AU - Wesseling, Pieter

AU - Carbo, Ellen W S

AU - Hillebrand, Arjan

AU - van Dellen, Edwin

AU - de Witt Hamer, Philip C

AU - Klein, Martin

AU - Schenk, Geert J

AU - Geurts, Jeroen J G

AU - Reijneveld, Jaap C

AU - Douw, Linda

PY - 2018/11

Y1 - 2018/11

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Biomarkers, Tumor/metabolism

KW - Brain/pathology

KW - Brain Neoplasms/diagnosis

KW - Brain Waves/physiology

KW - Cell Adhesion Molecules, Neuronal/metabolism

KW - Cohort Studies

KW - Disease Progression

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Glioma/diagnosis

KW - Humans

KW - Magnetoencephalography

KW - Male

KW - Membrane Proteins/metabolism

KW - Middle Aged

KW - Nerve Tissue Proteins/metabolism

KW - Prognosis

KW - Progression-Free Survival

U2 - 10.1007/s11060-018-2967-5

DO - 10.1007/s11060-018-2967-5

M3 - Article

VL - 140

SP - 403

EP - 412

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

SN - 0167-594X

IS - 2

ER -