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Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma

Epilepsy at presentation is an independent favorable prognostic factor in glioblastoma (GBM). In this study, we analyze the oncologic signaling pathways that associate with epilepsy in human GBMs, and that can underlie this prognostic effect. Following ethical approval and patient consent, fresh fro...

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Autores principales: Berendsen, Sharon, Spliet, Wim G. M., Geurts, Marjolein, Van Hecke, Wim, Seute, Tatjana, Snijders, Tom J., Bours, Vincent, Bell, Erica H., Chakravarti, Arnab, Robe, Pierre A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356242/
https://www.ncbi.nlm.nih.gov/pubmed/30621209
http://dx.doi.org/10.3390/cancers11010041
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author Berendsen, Sharon
Spliet, Wim G. M.
Geurts, Marjolein
Van Hecke, Wim
Seute, Tatjana
Snijders, Tom J.
Bours, Vincent
Bell, Erica H.
Chakravarti, Arnab
Robe, Pierre A.
author_facet Berendsen, Sharon
Spliet, Wim G. M.
Geurts, Marjolein
Van Hecke, Wim
Seute, Tatjana
Snijders, Tom J.
Bours, Vincent
Bell, Erica H.
Chakravarti, Arnab
Robe, Pierre A.
author_sort Berendsen, Sharon
collection PubMed
description Epilepsy at presentation is an independent favorable prognostic factor in glioblastoma (GBM). In this study, we analyze the oncologic signaling pathways that associate with epilepsy in human GBMs, and that can underlie this prognostic effect. Following ethical approval and patient consent, fresh frozen GBM tissue was obtained from 76 patient surgeries. Hospital records were screened for the presence of seizures at presentation of the disease. mRNA and miRNA expression-based and gene set enrichment analyses were performed on these tissues, to uncover candidate oncologic pathways that associate with epilepsy. We performed qPCR experiments and immunohistochemistry on tissue microarrays containing 286 GBMs to further explore the association of these candidate pathways and of markers of mesenchymal transformation (NF-κB, CEBP-β, STAT3, STAT5b, VEGFA, SRF) with epilepsy. Gene sets involved in hypoxia/HIF-1α, STAT5, CEBP-β and epithelial-mesenchymal transformation signaling were significantly downregulated in epileptogenic GBMs. On confirmatory protein expression analyses, epileptogenic tumors were characterized by a significant downregulation of phospho-STAT5b, a target of HIF-1α. Epilepsy status did not associate with molecular subclassification or miRNA expression patterns of the tumors. Epileptogenic GBMs correlate with decreased hypoxia/ HIF-1α/STAT5b signaling compared to glioblastomas that do not present with epilepsy.
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spelling pubmed-63562422019-02-05 Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma Berendsen, Sharon Spliet, Wim G. M. Geurts, Marjolein Van Hecke, Wim Seute, Tatjana Snijders, Tom J. Bours, Vincent Bell, Erica H. Chakravarti, Arnab Robe, Pierre A. Cancers (Basel) Article Epilepsy at presentation is an independent favorable prognostic factor in glioblastoma (GBM). In this study, we analyze the oncologic signaling pathways that associate with epilepsy in human GBMs, and that can underlie this prognostic effect. Following ethical approval and patient consent, fresh frozen GBM tissue was obtained from 76 patient surgeries. Hospital records were screened for the presence of seizures at presentation of the disease. mRNA and miRNA expression-based and gene set enrichment analyses were performed on these tissues, to uncover candidate oncologic pathways that associate with epilepsy. We performed qPCR experiments and immunohistochemistry on tissue microarrays containing 286 GBMs to further explore the association of these candidate pathways and of markers of mesenchymal transformation (NF-κB, CEBP-β, STAT3, STAT5b, VEGFA, SRF) with epilepsy. Gene sets involved in hypoxia/HIF-1α, STAT5, CEBP-β and epithelial-mesenchymal transformation signaling were significantly downregulated in epileptogenic GBMs. On confirmatory protein expression analyses, epileptogenic tumors were characterized by a significant downregulation of phospho-STAT5b, a target of HIF-1α. Epilepsy status did not associate with molecular subclassification or miRNA expression patterns of the tumors. Epileptogenic GBMs correlate with decreased hypoxia/ HIF-1α/STAT5b signaling compared to glioblastomas that do not present with epilepsy. MDPI 2019-01-04 /pmc/articles/PMC6356242/ /pubmed/30621209 http://dx.doi.org/10.3390/cancers11010041 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
Berendsen, Sharon
Spliet, Wim G. M.
Geurts, Marjolein
Van Hecke, Wim
Seute, Tatjana
Snijders, Tom J.
Bours, Vincent
Bell, Erica H.
Chakravarti, Arnab
Robe, Pierre A.
Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma
title Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma
title_full Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma
title_fullStr Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma
title_full_unstemmed Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma
title_short Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma
title_sort epilepsy associates with decreased hif-1α/stat5b signaling in glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356242/
https://www.ncbi.nlm.nih.gov/pubmed/30621209
http://dx.doi.org/10.3390/cancers11010041
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