The impact of neddylation on prognosis in the immune microenvironment of neuroblastoma: a single-cell transcriptomic analysis.

Abstract

Neuroblastoma (NB) is a prevalent malignant tumor in children, primarily affecting the nervous system, with a high mortality rate, particularly in high-risk patients. This study aims to establish a neddylation-related prognostic signature (NRPS) through the analysis of gene expression data from NB patients and to evaluate its clinical application potential. A comprehensive analysis was conducted using gene expression profiling, single-cell RNA sequencing (scRNA-seq), weighted gene co-expression network analysis (WGCNA), and single-sample gene set enrichment analysis (ssGSEA) to elucidate the role of neddylation and establish a NRPS for NB patients. Our analysis identified 171,992 cells categorized into 19 distinct clusters, revealing that Schwann and tumor cells exhibited significantly higher neddylation scores compared to other cell types. We constructed a NRPS that significantly impacts overall survival and event-free survival. Immune infiltration analysis demonstrated significantly higher levels of immune cells, particularly activated CD8 + T cells and natural killer cells, in the low-risk group, indicating a stronger anti-tumor immune response. Furthermore, gene set enrichment analysis (GSEA) revealed that the high-risk group was associated with cell division and DNA repair pathways, while the low-risk group showed enrichment in immune-related signaling pathways, suggesting immune activation may confer protective effects. Additionally, the immunotherapy analysis suggested that the low-risk score group exhibited better immunotherapy outcomes. This study underscores the clinical significance of NRPS in predicting survival and therapeutic outcomes in NB patients, highlighting their necessity and urgency in personalized treatment approaches.