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Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma

BACKGROUND: Neuroblastoma (NB) is a heterogeneous disease with respect to genomic abnormalities and clinical behaviors. Despite recent advances in our understanding of the association between the genetic aberrations and clinical features, it remains one of the major challenges to predict prognosis a...

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Autores principales: He, Xiaoyan, Qin, Chao, Zhao, Yanding, Zou, Lin, Zhao, Hui, Cheng, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163660/
https://www.ncbi.nlm.nih.gov/pubmed/32237073
http://dx.doi.org/10.1002/cac2.12016
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author He, Xiaoyan
Qin, Chao
Zhao, Yanding
Zou, Lin
Zhao, Hui
Cheng, Chao
author_facet He, Xiaoyan
Qin, Chao
Zhao, Yanding
Zou, Lin
Zhao, Hui
Cheng, Chao
author_sort He, Xiaoyan
collection PubMed
description BACKGROUND: Neuroblastoma (NB) is a heterogeneous disease with respect to genomic abnormalities and clinical behaviors. Despite recent advances in our understanding of the association between the genetic aberrations and clinical features, it remains one of the major challenges to predict prognosis and stratify patients for determining personalized therapy in this disease. The aim of this study was to develop an effective prognosis prediction model for NB patients. METHODS: We integrated diverse computational analyses to define gene signatures that reflect MYCN activity and chromosomal aberrations including deletion of chromosome 1p (Chr1p_del) and chromosome 11q (Chr11q_del) as well as chromosome 11q whole loss (Chr11q_wls). We evaluated the prognostic and predictive values of these signatures in seven NB gene expression datasets (the number of samples ranges from 94 to 498, with a total of 2120) generated from both RNA sequencing and microarray platforms. RESULTS: MYCN signature was a more effective prognostic marker than MYCN amplification status and MYCN expression. Similarly, the Chr1p_del score was more prognostic than Chr1p status. The activity scores of MYCN, Chr1p_del and Chr11q_del were associated with poor prognosis, while the Chr11q_wls score was linked to good outcome. We integrated the activity scores of MYCN, Chr1p_del, Chr11q_del, and Chr11q_wls and clinical variables into an integrative prognostic model, which displayed significant performance over the clinical variables or each genomic aberration alone. CONCLUSIONS: Our integrative gene signature model shows a significantly improved forecast performance with prognostic and predictive information, and thereby can be served as a biomarker to stratify NB patients for prognosis evaluation and surveillance programs.
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spelling pubmed-71636602020-04-20 Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma He, Xiaoyan Qin, Chao Zhao, Yanding Zou, Lin Zhao, Hui Cheng, Chao Cancer Commun (Lond) Original Articles BACKGROUND: Neuroblastoma (NB) is a heterogeneous disease with respect to genomic abnormalities and clinical behaviors. Despite recent advances in our understanding of the association between the genetic aberrations and clinical features, it remains one of the major challenges to predict prognosis and stratify patients for determining personalized therapy in this disease. The aim of this study was to develop an effective prognosis prediction model for NB patients. METHODS: We integrated diverse computational analyses to define gene signatures that reflect MYCN activity and chromosomal aberrations including deletion of chromosome 1p (Chr1p_del) and chromosome 11q (Chr11q_del) as well as chromosome 11q whole loss (Chr11q_wls). We evaluated the prognostic and predictive values of these signatures in seven NB gene expression datasets (the number of samples ranges from 94 to 498, with a total of 2120) generated from both RNA sequencing and microarray platforms. RESULTS: MYCN signature was a more effective prognostic marker than MYCN amplification status and MYCN expression. Similarly, the Chr1p_del score was more prognostic than Chr1p status. The activity scores of MYCN, Chr1p_del and Chr11q_del were associated with poor prognosis, while the Chr11q_wls score was linked to good outcome. We integrated the activity scores of MYCN, Chr1p_del, Chr11q_del, and Chr11q_wls and clinical variables into an integrative prognostic model, which displayed significant performance over the clinical variables or each genomic aberration alone. CONCLUSIONS: Our integrative gene signature model shows a significantly improved forecast performance with prognostic and predictive information, and thereby can be served as a biomarker to stratify NB patients for prognosis evaluation and surveillance programs. John Wiley and Sons Inc. 2020-03-31 /pmc/articles/PMC7163660/ /pubmed/32237073 http://dx.doi.org/10.1002/cac2.12016 Text en © 2020 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat‐sen University Cancer Center This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
He, Xiaoyan
Qin, Chao
Zhao, Yanding
Zou, Lin
Zhao, Hui
Cheng, Chao
Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma
title Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma
title_full Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma
title_fullStr Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma
title_full_unstemmed Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma
title_short Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma
title_sort gene signatures associated with genomic aberrations predict prognosis in neuroblastoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163660/
https://www.ncbi.nlm.nih.gov/pubmed/32237073
http://dx.doi.org/10.1002/cac2.12016
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