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Duchenne muscular dystrophy gene expression is an independent prognostic marker for IDH mutant low-grade glioma

Alterations in the expression of the Duchenne muscular dystrophy (DMD) gene have been associated with the development, progression and survival outcomes of numerous cancers including tumours of the central nervous system. We undertook a detailed bioinformatic analysis of low-grade glioma (LGG) bulk...

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Autores principales: Naidoo, Michael, Jones, Leanne, Conboy, Benjamin, Hamarneh, Wael, D’Souza, Darwin, Anthony, Karen, Machado, Lee R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881458/
https://www.ncbi.nlm.nih.gov/pubmed/35217778
http://dx.doi.org/10.1038/s41598-022-07223-2
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author Naidoo, Michael
Jones, Leanne
Conboy, Benjamin
Hamarneh, Wael
D’Souza, Darwin
Anthony, Karen
Machado, Lee R.
author_facet Naidoo, Michael
Jones, Leanne
Conboy, Benjamin
Hamarneh, Wael
D’Souza, Darwin
Anthony, Karen
Machado, Lee R.
author_sort Naidoo, Michael
collection PubMed
description Alterations in the expression of the Duchenne muscular dystrophy (DMD) gene have been associated with the development, progression and survival outcomes of numerous cancers including tumours of the central nervous system. We undertook a detailed bioinformatic analysis of low-grade glioma (LGG) bulk RNAseq data to characterise the association between DMD expression and LGG survival outcomes. High DMD expression was significantly associated with poor survival in LGG with a difference in median overall survival between high and low DMD groups of over 7 years (P = < 0.0001). In a multivariate model, DMD expression remained significant (P = 0.02) and was an independent prognostic marker for LGG. The effect of DMD expression on overall survival was only apparent in isocitrate dehydrogenase (IDH) mutant cases where non-1p/19q co-deleted LGG patients could be further stratified into high/low DMD groups. Patients in the high DMD group had a median overall survival time almost halve that of the low DMD group. The expression of the individual DMD gene products Dp71, Dp71ab and Dp427m were also significantly associated with overall survival in LGG which have differential biological effects relevant to the pathogenesis of LGG. Differential gene expression and pathway analysis identifies dysregulated biological processes relating to ribosome biogenesis, synaptic signalling, neurodevelopment, morphogenesis and immune pathways. Genes spanning almost the entirety of chromosome 1p are upregulated in patients with high overall DMD, Dp71 and Dp427m expression which worsens survival outcomes for these patients. We confirmed dystrophin protein is variably expressed in LGG tumour tissue by immunohistochemistry and, overall, demonstrate that DMD expression has potential utility as an independent prognostic marker which can further stratify IDH mutant LGG to identify those at risk of poor survival. This knowledge may improve risk stratification and management of LGG.
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spelling pubmed-88814582022-03-01 Duchenne muscular dystrophy gene expression is an independent prognostic marker for IDH mutant low-grade glioma Naidoo, Michael Jones, Leanne Conboy, Benjamin Hamarneh, Wael D’Souza, Darwin Anthony, Karen Machado, Lee R. Sci Rep Article Alterations in the expression of the Duchenne muscular dystrophy (DMD) gene have been associated with the development, progression and survival outcomes of numerous cancers including tumours of the central nervous system. We undertook a detailed bioinformatic analysis of low-grade glioma (LGG) bulk RNAseq data to characterise the association between DMD expression and LGG survival outcomes. High DMD expression was significantly associated with poor survival in LGG with a difference in median overall survival between high and low DMD groups of over 7 years (P = < 0.0001). In a multivariate model, DMD expression remained significant (P = 0.02) and was an independent prognostic marker for LGG. The effect of DMD expression on overall survival was only apparent in isocitrate dehydrogenase (IDH) mutant cases where non-1p/19q co-deleted LGG patients could be further stratified into high/low DMD groups. Patients in the high DMD group had a median overall survival time almost halve that of the low DMD group. The expression of the individual DMD gene products Dp71, Dp71ab and Dp427m were also significantly associated with overall survival in LGG which have differential biological effects relevant to the pathogenesis of LGG. Differential gene expression and pathway analysis identifies dysregulated biological processes relating to ribosome biogenesis, synaptic signalling, neurodevelopment, morphogenesis and immune pathways. Genes spanning almost the entirety of chromosome 1p are upregulated in patients with high overall DMD, Dp71 and Dp427m expression which worsens survival outcomes for these patients. We confirmed dystrophin protein is variably expressed in LGG tumour tissue by immunohistochemistry and, overall, demonstrate that DMD expression has potential utility as an independent prognostic marker which can further stratify IDH mutant LGG to identify those at risk of poor survival. This knowledge may improve risk stratification and management of LGG. Nature Publishing Group UK 2022-02-25 /pmc/articles/PMC8881458/ /pubmed/35217778 http://dx.doi.org/10.1038/s41598-022-07223-2 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, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Naidoo, Michael
Jones, Leanne
Conboy, Benjamin
Hamarneh, Wael
D’Souza, Darwin
Anthony, Karen
Machado, Lee R.
Duchenne muscular dystrophy gene expression is an independent prognostic marker for IDH mutant low-grade glioma
title Duchenne muscular dystrophy gene expression is an independent prognostic marker for IDH mutant low-grade glioma
title_full Duchenne muscular dystrophy gene expression is an independent prognostic marker for IDH mutant low-grade glioma
title_fullStr Duchenne muscular dystrophy gene expression is an independent prognostic marker for IDH mutant low-grade glioma
title_full_unstemmed Duchenne muscular dystrophy gene expression is an independent prognostic marker for IDH mutant low-grade glioma
title_short Duchenne muscular dystrophy gene expression is an independent prognostic marker for IDH mutant low-grade glioma
title_sort duchenne muscular dystrophy gene expression is an independent prognostic marker for idh mutant low-grade glioma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881458/
https://www.ncbi.nlm.nih.gov/pubmed/35217778
http://dx.doi.org/10.1038/s41598-022-07223-2
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