Development and Validation of a Five-RNA-Based Signature and Identification of Candidate Drugs for Neuroblastoma

PeiPei Zhang; KeXin Ma; XiaoFei Ke; Liu Liu; Ying Li; YaJuan Liu; YouJun Wang

doi:10.3389/fgene.2021.685646

Development and Validation of a Five-RNA-Based Signature and Identification of Candidate Drugs for Neuroblastoma

Front Genet. 2021 Oct 20:12:685646. doi: 10.3389/fgene.2021.685646. eCollection 2021.

Authors

PeiPei Zhang¹, KeXin Ma¹, XiaoFei Ke¹, Liu Liu¹, Ying Li¹, YaJuan Liu¹, YouJun Wang¹

Affiliation

¹ Department of Pediatrics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

Abstract

Neuroblastoma (NBL) originating from the sympathetic nervous system is the most prevalent solid tumor in infancy. Although there is sufficient variability in prognosis among different age pyramids, age-related gene expression profiles and biomarkers remain poorly explored. The present study aimed to construct a signature based on differentially expressed genes (DEGs) between two age groups in NBL. Univariate Cox regression, multivariate Cox regression, and LASSO analyses were used to identify the optimal prognostic factors. The prediction ability of the model was assessed using the receiver operating characteristic (ROC) curve and C-index. Functional enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes and gene ontology databases. A total of 1,160 DEGs were identified between the two groups, and 204 DEGs impacted the survival of NBL. Functional enrichment analysis revealed that the DEGs were involved in retinol metabolism, cholesterol metabolism, and glycolysis/gluconeogenesis pathways. Five RNAs, namely F8A3, PDF, ANKRD24, FAXDC2, and TMEM160 were recruited into the signature. They were correlated with COG risk classification, INSS stage, and histology. MYCN amplification was linked to FAXDC2, TMEM160, PDF, and F8A3. The expression levels of ANKRD24, PDF, and TMEM160 were lower in the hyperdiploid groups. Only FAXDC2 levels were different in the different MKI grades. The ROC curve showed that the five-RNA-based signatures effectively predicted the OS of NBL (3-years AUC = 0.791, 5-years AUC = 0.816) in the TARGET cohort. The predictive capability was also validated by the GSE49711 cohort (3-years AUC = 0.851, 5-years AUC = 0.848). The C-index in the TARGET and GSE49711 cohorts was 0.749 and 0.809, respectively. The potential mechanisms of the five RNAs were also explored via gene set enrichment analysis, and candidate drugs targeting the five genes, including dabrafenib, vemurafenib, and bafetinib, were screened. In conclusion, we constructed a five-RNA-based signature to predict the survival of NBL and screened candidate agents against NBL.

Keywords: Neuroblastoma; Signature; age; drugs; prognosis.