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Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma
- Source :
- Cancer Communications
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Oncology
Male
Cancer Research
medicine.medical_specialty
Microarray
Adolescent
Disease
Chromosome aberration
survival analysis
03 medical and health sciences
neuroblastoma
0302 clinical medicine
Neuroblastoma
Internal medicine
Medicine
Humans
Child
Gene
neoplasms
Survival analysis
Chromosome Aberrations
N-Myc Proto-Oncogene Protein
business.industry
Chromosomes, Human, Pair 11
Gene Amplification
Infant, Newborn
Infant
Genomics
Original Articles
Gene signature
medicine.disease
Prognosis
030104 developmental biology
Chromosomes, Human, Pair 1
030220 oncology & carcinogenesis
Child, Preschool
MYCN gene
Biomarker (medicine)
gene expression profile
Female
Original Article
chromosome aberration
business
Subjects
Details
- ISSN :
- 25233548
- Volume :
- 40
- Issue :
- 2-3
- Database :
- OpenAIRE
- Journal :
- Cancer communications (London, England)
- Accession number :
- edsair.doi.dedup.....1f07eb4507dd6c4d0c436dc5a5cf43bf