High-risk, Expression-Based Prognostic Long Noncoding RNA Signature in Neuroblastoma
Journal
JNCI cancer spectrum
Journal Volume
2
Journal Issue
2
Pages
pky015
Date Issued
2018
Author(s)
Abstract
Background: Current clinical risk factors stratify patients with neuroblastoma (NB) for appropriate treatments, yet patients with similar clinical behaviors evoke variable responses. MYCN amplification is one of the established drivers of NB and, when combined with high-risk displays, worsens outcomes. Growing high-throughput transcriptomics studies suggest long noncoding RNA (lncRNA) dysregulation in cancers, including NB. However, expression-based lncRNA signatures are altered by MYCN amplification, which is associated with high-risk, and patient prognosis remains limited. Methods: We investigated RNA-seq-based expression profiles of lncRNAs in MYCN status and risk status in a discovery cohort (n = 493) and validated them in three independent cohorts. In the discovery cohort, a prognostic association of lncRNAs was determined by univariate Cox regression and integrated into a signature using the risk score method. A novel risk score threshold selection criterion was developed to stratify patients into risk groups. Outcomes by risk group and clinical subgroup were assessed using Kaplan-Meier survival curves and multivariable Cox regression. The performance of lncRNA signatures was evaluated by receiver operating characteristic curve. All statistical tests were two-sided. Results: In the discovery cohort, 16 lncRNAs that were differentially expressed (fold change ? 2 and adjusted P ? 0.01) integrated into a prognostic signature. A high risk score group of lncRNA signature had poor event-free survival (EFS; P < 1E-16). Notably, lncRNA signature was independent of other clinical risk factors when predicting EFS (hazard ratio = 3.21, P = 5.95E-07). The findings were confirmed in independent cohorts (P = 2.86E-02, P = 6.18E-03, P = 9.39E-03, respectively). Finally, the lncRNA signature had higher accuracy for EFS prediction (area under the curve = 0.788, 95% confidence interval = 0.746 to 0.831). Conclusions: Here, we report the first (to our knowledge) RNA-seq 16-lncRNA prognostic signature for NB that may contribute to precise clinical stratification and EFS prediction. ? The Author(s) 2018.
SDGs
Other Subjects
tumor marker; untranslated RNA; Article; cancer prognosis; cancer survival; cohort analysis; controlled study; diagnostic accuracy; diagnostic test accuracy study; event free survival; gene amplification; gene expression; gene identification; genetic analysis; human; infant; major clinical study; neuroblastoma; overall survival; predictive value; priority journal; prognostic assessment; receiver operating characteristic; risk factor; RNA sequence; sensitivity and specificity
Publisher
Oxford University Press
Type
journal article