Epilepsy associates with decreased HIF-1α/STAT5b signaling in glioblastoma

[en] 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-17alpha;/STAT5b signaling compared to glioblastomas that do not present with epilepsy. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Disciplines :

Genetics & genetic processes

Author, co-author :

Berendsen, S.; Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center of Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands

Spliet, W. G. M.; Department of Pathology, University Medical Center of Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands

Geurts, M.; Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center of Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands

Van Hecke, W.; Department of Pathology, University Medical Center of Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands

Seute, T.; Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center of Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands

Snijders, T. J.; Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center of Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands

Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique humaine

Bell, E. H.; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital, The Ohio State University, West 10th Avenue, Columbus, OH 43210, United States

Chakravarti, A.; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital, The Ohio State University, West 10th Avenue, Columbus, OH 43210, United States

Robe, Pierre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques

Language :

English

Title :

Epilepsy associates with decreased HIF-1α/STAT5b signaling in glioblastoma

Publication date :

2019

Journal title :

Cancers

eISSN :

2072-6694

Publisher :

MDPI AG

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 08 February 2020

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