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Expression of decitabine-targeted oncogenes in meningiomas in vivo

Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine (DCT, 5-aza-2’–deoxycytidine) to be effective in high-grade meningiomas and, moreover, to induce hypomethylation of distinct o...

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Autores principales: Canisius, Julian, Wagner, Andrea, Bunk, Eva Christina, Spille, Dorothee Cäcilia, Stögbauer, Louise, Grauer, Oliver, Hess, Katharina, Thomas, Christian, Paulus, Werner, Stummer, Walter, Senner, Volker, Brokinkel, Benjamin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349086/
https://www.ncbi.nlm.nih.gov/pubmed/35445910
http://dx.doi.org/10.1007/s10143-022-01789-1
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author Canisius, Julian
Wagner, Andrea
Bunk, Eva Christina
Spille, Dorothee Cäcilia
Stögbauer, Louise
Grauer, Oliver
Hess, Katharina
Thomas, Christian
Paulus, Werner
Stummer, Walter
Senner, Volker
Brokinkel, Benjamin
author_facet Canisius, Julian
Wagner, Andrea
Bunk, Eva Christina
Spille, Dorothee Cäcilia
Stögbauer, Louise
Grauer, Oliver
Hess, Katharina
Thomas, Christian
Paulus, Werner
Stummer, Walter
Senner, Volker
Brokinkel, Benjamin
author_sort Canisius, Julian
collection PubMed
description Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine (DCT, 5-aza-2’–deoxycytidine) to be effective in high-grade meningiomas and, moreover, to induce hypomethylation of distinct oncogenes only sparsely described in meningiomas in vivo yet. Expression of the corresponding onco- and tumor suppressor genes TRIM58, FAM84B, ELOVL2, MAL2, LMO3, and DIO3 were analyzed and scored by immunohistochemical staining and RT-PCR in samples of 111 meningioma patients. Correlations with clinical and histological variables and prognosis were analyzed in uni- and multivariate analyses. All analyzed oncogenes were highly expressed in meningiomas. Expression scores of TRIM58 tended to be higher in benign than in high-grade tumors 20 vs 16 (p = .002) and all 9 samples lacking TRIM58 expression displayed WHO grade II/III histology. In contrast, median expression scores for both FAM84B (6 vs 4, p ≤ .001) and ELOVL2 (9 vs 6, p < .001) were increased in high-grade as compared to benign meningiomas. DIO3 expression was distinctly higher in all analyzed samples as compared to the reference decitabine-resistant Ben-Men 1 cell line. Increased ELOVL2 expression (score ≥ 8) correlated with tumor relapse in both uni- (HR: 2.42, 95%CI 1.18–4.94; p = .015) and multivariate (HR: 2.09, 95%CI 1.01–4.44; p = .046) analyses. All oncogenes involved in DCT efficacy in vitro are also widely expressed in vivo, and expression is partially associated with histology and prognosis. These results strongly encourage further analyses of DCT efficiency in meningiomas in vitro and in situ. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10143-022-01789-1.
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spelling pubmed-93490862022-08-05 Expression of decitabine-targeted oncogenes in meningiomas in vivo Canisius, Julian Wagner, Andrea Bunk, Eva Christina Spille, Dorothee Cäcilia Stögbauer, Louise Grauer, Oliver Hess, Katharina Thomas, Christian Paulus, Werner Stummer, Walter Senner, Volker Brokinkel, Benjamin Neurosurg Rev Original Article Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine (DCT, 5-aza-2’–deoxycytidine) to be effective in high-grade meningiomas and, moreover, to induce hypomethylation of distinct oncogenes only sparsely described in meningiomas in vivo yet. Expression of the corresponding onco- and tumor suppressor genes TRIM58, FAM84B, ELOVL2, MAL2, LMO3, and DIO3 were analyzed and scored by immunohistochemical staining and RT-PCR in samples of 111 meningioma patients. Correlations with clinical and histological variables and prognosis were analyzed in uni- and multivariate analyses. All analyzed oncogenes were highly expressed in meningiomas. Expression scores of TRIM58 tended to be higher in benign than in high-grade tumors 20 vs 16 (p = .002) and all 9 samples lacking TRIM58 expression displayed WHO grade II/III histology. In contrast, median expression scores for both FAM84B (6 vs 4, p ≤ .001) and ELOVL2 (9 vs 6, p < .001) were increased in high-grade as compared to benign meningiomas. DIO3 expression was distinctly higher in all analyzed samples as compared to the reference decitabine-resistant Ben-Men 1 cell line. Increased ELOVL2 expression (score ≥ 8) correlated with tumor relapse in both uni- (HR: 2.42, 95%CI 1.18–4.94; p = .015) and multivariate (HR: 2.09, 95%CI 1.01–4.44; p = .046) analyses. All oncogenes involved in DCT efficacy in vitro are also widely expressed in vivo, and expression is partially associated with histology and prognosis. These results strongly encourage further analyses of DCT efficiency in meningiomas in vitro and in situ. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10143-022-01789-1. Springer Berlin Heidelberg 2022-04-21 2022 /pmc/articles/PMC9349086/ /pubmed/35445910 http://dx.doi.org/10.1007/s10143-022-01789-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Canisius, Julian
Wagner, Andrea
Bunk, Eva Christina
Spille, Dorothee Cäcilia
Stögbauer, Louise
Grauer, Oliver
Hess, Katharina
Thomas, Christian
Paulus, Werner
Stummer, Walter
Senner, Volker
Brokinkel, Benjamin
Expression of decitabine-targeted oncogenes in meningiomas in vivo
title Expression of decitabine-targeted oncogenes in meningiomas in vivo
title_full Expression of decitabine-targeted oncogenes in meningiomas in vivo
title_fullStr Expression of decitabine-targeted oncogenes in meningiomas in vivo
title_full_unstemmed Expression of decitabine-targeted oncogenes in meningiomas in vivo
title_short Expression of decitabine-targeted oncogenes in meningiomas in vivo
title_sort expression of decitabine-targeted oncogenes in meningiomas in vivo
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349086/
https://www.ncbi.nlm.nih.gov/pubmed/35445910
http://dx.doi.org/10.1007/s10143-022-01789-1
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