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A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer

BACKGROUND: Gene expression can be employed for the discovery of prognostic gene or multigene signatures cancer. In this study, we assessed the prognostic value of a 35-gene expression signature selected by pathway and machine learning based methods in adjuvant therapy-linked glioblastoma multiforme...

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Autores principales: Fatai, Azeez A., Gamieldien, Junaid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883543/
https://www.ncbi.nlm.nih.gov/pubmed/29614978
http://dx.doi.org/10.1186/s12885-018-4103-5
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author Fatai, Azeez A.
Gamieldien, Junaid
author_facet Fatai, Azeez A.
Gamieldien, Junaid
author_sort Fatai, Azeez A.
collection PubMed
description BACKGROUND: Gene expression can be employed for the discovery of prognostic gene or multigene signatures cancer. In this study, we assessed the prognostic value of a 35-gene expression signature selected by pathway and machine learning based methods in adjuvant therapy-linked glioblastoma multiforme (GBM) patients from the Cancer Genome Atlas. METHODS: Genes with high expression variance was subjected to pathway enrichment analysis and those having roles in chemoradioresistance pathways were used in expression-based feature selection. A modified Support Vector Machine Recursive Feature Elimination algorithm was employed to select a subset of these genes that discriminated between rapidly-progressing and slowly-progressing patients. RESULTS: Survival analysis on TCGA samples not used in feature selection and samples from four GBM subclasses, as well as from an entirely independent study, showed that the 35-gene signature discriminated between the survival groups in all cases (p<0.05) and could accurately predict survival irrespective of the subtype. In a multivariate analysis, the signature predicted progression-free and overall survival independently of other factors considered. CONCLUSION: We propose that the performance of the signature makes it an attractive candidate for further studies to assess its utility as a clinical prognostic and predictive biomarker in GBM patients. Additionally, the signature genes may also be useful therapeutic targets to improve both progression-free and overall survival in GBM patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4103-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-58835432018-04-09 A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer Fatai, Azeez A. Gamieldien, Junaid BMC Cancer Research Article BACKGROUND: Gene expression can be employed for the discovery of prognostic gene or multigene signatures cancer. In this study, we assessed the prognostic value of a 35-gene expression signature selected by pathway and machine learning based methods in adjuvant therapy-linked glioblastoma multiforme (GBM) patients from the Cancer Genome Atlas. METHODS: Genes with high expression variance was subjected to pathway enrichment analysis and those having roles in chemoradioresistance pathways were used in expression-based feature selection. A modified Support Vector Machine Recursive Feature Elimination algorithm was employed to select a subset of these genes that discriminated between rapidly-progressing and slowly-progressing patients. RESULTS: Survival analysis on TCGA samples not used in feature selection and samples from four GBM subclasses, as well as from an entirely independent study, showed that the 35-gene signature discriminated between the survival groups in all cases (p<0.05) and could accurately predict survival irrespective of the subtype. In a multivariate analysis, the signature predicted progression-free and overall survival independently of other factors considered. CONCLUSION: We propose that the performance of the signature makes it an attractive candidate for further studies to assess its utility as a clinical prognostic and predictive biomarker in GBM patients. Additionally, the signature genes may also be useful therapeutic targets to improve both progression-free and overall survival in GBM patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4103-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-03 /pmc/articles/PMC5883543/ /pubmed/29614978 http://dx.doi.org/10.1186/s12885-018-4103-5 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Fatai, Azeez A.
Gamieldien, Junaid
A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer
title A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer
title_full A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer
title_fullStr A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer
title_full_unstemmed A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer
title_short A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer
title_sort 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883543/
https://www.ncbi.nlm.nih.gov/pubmed/29614978
http://dx.doi.org/10.1186/s12885-018-4103-5
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