Abstract
Background: Neuroblastoma (NB), the most common solid tumor in children, exhibits vastly different genomic abnormalities and clinical behaviors. While significant progress has been made on the research of relations between clinical manifestations and genetic abnormalities, it remains a major challenge to predict the prognosis of patients to facilitate personalized treatments. Materials and Methods: Six data sets of gene expression and related clinical data were downloaded from the Gene Expression Omnibus (GEO) database, ArrayExpress database, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to the presence or absence of MYCN amplification, patients were divided into two groups. Differentially expressed genes (DEGs) were identified between the two groups. Enrichment analyses of these DEGs were performed to dig further into the molecular mechanism of NB. Stepwise Cox regression analyses were used to establish a five-gene prognostic signature whose predictive performance was further evaluated by external validation. Multivariate Cox regression analyses were used to explore independent prognostic factors for NB. The relevance of immunity was evaluated by using algorithms, and a nomogram was constructed. Results: A five-gene signature comprising CPLX3, GDPD5, SPAG6, NXPH1, and AHI1 was established. The five-gene signature had good performance in predicting survival and was demonstrated to be superior to International Neuroblastoma Staging System (INSS) staging and the MYCN amplification status. Finally, a nomogram based on the five-gene signature was established, and its clinical efficacy was demonstrated. Conclusion: Collectively, our study developed a novel five-gene signature and successfully built a prognostic nomogram that accurately predicted survival in NB. The findings presented here could help to stratify patients into subgroups and determine the optimal individualized therapy.
Highlights
Neuroblastoma (NB) is the most common extracranial solid tumor in children, with the highest incidence and mortality in infancy, accounting for approximately 8–10% of pediatric malignancies (Li et al, 2008; Marshall et al, 2014)
Detailed information on the Gene Expression Omnibus (GEO), TARGET, and ArrayExpress data sets in this project is shown in Supplementary Table S2
Through the robust rank aggregation (RRA) method, DEGs derived from four data sets were integrated and analyzed
Summary
Neuroblastoma (NB) is the most common extracranial solid tumor in children, with the highest incidence and mortality in infancy, accounting for approximately 8–10% of pediatric malignancies (Li et al, 2008; Marshall et al, 2014) It is a highly heterogeneous disease characterized by diverse clinical manifestations ranging from spontaneous regression to progression with therapy resistance. There is increasing evidence that several genomic alterations, such as gain of chromosome 17q, hemizygous deletions of 1p and 11q, and MYCN gene amplification, are powerful prognostic markers that are strongly associated with clinical outcomes (Janoueix-Lerosey et al, 2009; Maris, 2010; Schleiermacher et al, 2012). While significant progress has been made on the research of relations between clinical manifestations and genetic abnormalities, it remains a major challenge to predict the prognosis of patients to facilitate personalized treatments
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
