Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma.
MYCN gene
chromosome aberration
gene expression profile
neuroblastoma
prognosis
survival analysis
Journal
Cancer communications (London, England)
ISSN: 2523-3548
Titre abrégé: Cancer Commun (Lond)
Pays: United States
ID NLM: 101723675
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
06
01
2020
accepted:
13
02
2020
entrez:
3
4
2020
pubmed:
3
4
2020
medline:
26
3
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32237073
doi: 10.1002/cac2.12016
pmc: PMC7163660
doi:
Substances chimiques
MYCN protein, human
0
N-Myc Proto-Oncogene Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105-118Subventions
Organisme : NCI NIH HHS
ID : P30 CA023108
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001088
Pays : United States
Informations de copyright
© 2020 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.
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Cancer Commun (Lond). 2020 Mar;40(2-3):105-118
pubmed: 32237073