Abstract
Background and Objective: Neuroblastoma (NB), the most common pediatric solid tumor apart from brain tumor, is associated with dismal long-term survival. The aim of this study was to identify a gene signature to predict the prognosis of NB patients.Materials and Methods: GSE49710 dataset from the Gene Expression Omnibus (GEO) database was downloaded and differentially expressed genes (DEGs) were analyzed using R package “limma” and SPSS software. The gene ontology (GO) and pathway enrichment analysis were established via DAVID database. Random forest (RF) and risk score model were used to pick out the gene signature in predicting the prognosis of NB patients. Simultaneously, the receiving operating characteristic (ROC) and Kaplan-Meier curve were plotted. GSE45480 and GSE16476 datasets were employed to validate the robustness of the gene signature.Results: A total of 131 DEGs were identified, which were mainly enriched in cancer-related pathways. Four genes (ERCC6L, AHCY, STK33, and NCAN) were selected as a gene signature, which was included in the top six important features in RF model, to predict the prognosis in NB patients, its area under the curve (AUC) could reach 0.86, and Cox regression analysis revealed that the 4-gene signature was an independent prognostic factor of overall survival and event-free survival. As well as in GSE16476. Additionally, the robustness of discriminating different groups of the 4-gene signature was verified to have a commendable performance in GSE45480 and GSE49710.Conclusion: The present study identified a gene-signature in predicting the prognosis in NB, which may provide novel prognostic markers, and some of the genes may be as treatment targets according to biological experiments in the future.
Highlights
Neuroblastoma (NB) is a highly heterogeneous pediatric solid tumor both in clinical and biological characteristics
We have identified a four-gene signature via Random forest (RF) and risk score model in predicting the prognosis of NB patients via the GEO dataset (GSE49710), the gene signature had good performance in discriminating other groups of GSE49710, as well as in other two independent datasets
Stage 4s patients with MYCN amplification, high risk and death from disease had occupied less than 4.5%, and those with progression had accounted for 7.5%
Summary
Neuroblastoma (NB) is a highly heterogeneous pediatric solid tumor both in clinical and biological characteristics. It is the third most common malignant disease, which takes about 7% of malignant tumors in children less than 14 years, with the incidence of close to 60/100,000 during the first year of life (Maris et al, 2007; Sausen et al, 2013; Ward et al, 2014). Neuroblastoma (NB), the most common pediatric solid tumor apart from brain tumor, is associated with dismal long-term survival. The aim of this study was to identify a gene signature to predict the prognosis of NB patients
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