Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas

Abstract Distant intercellular communication in gliomas is based on the expansion of tumor microtubuli, where actin forms cytoskeleton and GAP-43 mediates the axonal conus growth. We aimed to investigate the impact of GAP-43 and actin expression on overall survival (OS) as well as crucial prognostic...

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Main Authors: Aleksandrs Krigers, Matthias Demetz, Patrizia Moser, Johannes Kerschbaumer, Konstantin R. Brawanski, Helga Fritsch, Claudius Thomé, Christian F. Freyschlag
Format: Article
Language:English
Published: Nature Portfolio 2023-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-29298-1
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author Aleksandrs Krigers
Matthias Demetz
Patrizia Moser
Johannes Kerschbaumer
Konstantin R. Brawanski
Helga Fritsch
Claudius Thomé
Christian F. Freyschlag
author_facet Aleksandrs Krigers
Matthias Demetz
Patrizia Moser
Johannes Kerschbaumer
Konstantin R. Brawanski
Helga Fritsch
Claudius Thomé
Christian F. Freyschlag
author_sort Aleksandrs Krigers
collection DOAJ
description Abstract Distant intercellular communication in gliomas is based on the expansion of tumor microtubuli, where actin forms cytoskeleton and GAP-43 mediates the axonal conus growth. We aimed to investigate the impact of GAP-43 and actin expression on overall survival (OS) as well as crucial prognostic factors. FFPE tissue of adult patients with diffuse and anaplastic gliomas, who underwent first surgery in our center between 2010 and 2019, were selected. GAP-43, Cx43 and actin expression was analyzed using immunohistochemistry and semi-quantitatively ranked. 118 patients with a median age of 46 years (IqR: 35–57) were evaluated. 48 (41%) presented with a diffuse glioma and 70 (59%) revealed anaplasia. Tumors with higher expression of GAP-43 (p = 0.024, HR = 1.71/rank) and actin (p < 0.001, HR = 2.28/rank) showed significantly reduced OS. IDH1 wildtype glioma demonstrated significantly more expression of all proteins: GAP-43 (p = 0.009), Cx43 (p = 0.003) and actin (p < 0.001). The same was confirmed for anaplasia (GAP-43 p = 0.028, actin p = 0.029), higher proliferation rate (GAP-43 p = 0.016, actin p = 0.038), contrast-enhancement in MRI (GAP-43 p = 0.023, actin p = 0.037) and age (GAP-43 p = 0.004, actin p < 0.001; Cx43 n.s. in all groups). The intercellular distant communication network in diffuse and anaplastic gliomas formed by actin and GAP-43 is associated with a negative impact on overall survival and with unfavorable prognostic features. Cx43 did not show relevant impact on OS.
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spelling doaj.art-f6504bef33dd4d28ac9e8d1d8971c3ea2023-02-05T12:09:43ZengNature PortfolioScientific Reports2045-23222023-02-011311910.1038/s41598-023-29298-1Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomasAleksandrs Krigers0Matthias Demetz1Patrizia Moser2Johannes Kerschbaumer3Konstantin R. Brawanski4Helga Fritsch5Claudius Thomé6Christian F. Freyschlag7Department of Neurosurgery, Medical University of InnsbruckDepartment of Neurosurgery, Medical University of InnsbruckDepartment of Neuropathology, University Hospital of InnsbruckDepartment of Neurosurgery, Medical University of InnsbruckDepartment of Neurosurgery, Medical University of InnsbruckDepartment of Anatomy, Histology and Embryology, Medical University of InnsbruckDepartment of Neurosurgery, Medical University of InnsbruckDepartment of Neurosurgery, Medical University of InnsbruckAbstract Distant intercellular communication in gliomas is based on the expansion of tumor microtubuli, where actin forms cytoskeleton and GAP-43 mediates the axonal conus growth. We aimed to investigate the impact of GAP-43 and actin expression on overall survival (OS) as well as crucial prognostic factors. FFPE tissue of adult patients with diffuse and anaplastic gliomas, who underwent first surgery in our center between 2010 and 2019, were selected. GAP-43, Cx43 and actin expression was analyzed using immunohistochemistry and semi-quantitatively ranked. 118 patients with a median age of 46 years (IqR: 35–57) were evaluated. 48 (41%) presented with a diffuse glioma and 70 (59%) revealed anaplasia. Tumors with higher expression of GAP-43 (p = 0.024, HR = 1.71/rank) and actin (p < 0.001, HR = 2.28/rank) showed significantly reduced OS. IDH1 wildtype glioma demonstrated significantly more expression of all proteins: GAP-43 (p = 0.009), Cx43 (p = 0.003) and actin (p < 0.001). The same was confirmed for anaplasia (GAP-43 p = 0.028, actin p = 0.029), higher proliferation rate (GAP-43 p = 0.016, actin p = 0.038), contrast-enhancement in MRI (GAP-43 p = 0.023, actin p = 0.037) and age (GAP-43 p = 0.004, actin p < 0.001; Cx43 n.s. in all groups). The intercellular distant communication network in diffuse and anaplastic gliomas formed by actin and GAP-43 is associated with a negative impact on overall survival and with unfavorable prognostic features. Cx43 did not show relevant impact on OS.https://doi.org/10.1038/s41598-023-29298-1
spellingShingle Aleksandrs Krigers
Matthias Demetz
Patrizia Moser
Johannes Kerschbaumer
Konstantin R. Brawanski
Helga Fritsch
Claudius Thomé
Christian F. Freyschlag
Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas
Scientific Reports
title Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas
title_full Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas
title_fullStr Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas
title_full_unstemmed Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas
title_short Impact of GAP-43, Cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas
title_sort impact of gap 43 cx43 and actin expression on the outcome and overall survival in diffuse and anaplastic gliomas
url https://doi.org/10.1038/s41598-023-29298-1
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