Prognosis and immune infiltration prediction in neuroblastoma based on neutrophil extracellular traps-related gene signature

Abstract

Abstract Neuroblastoma (NB) is a malignant tumor originating from the peripheral sympathetic nervous system and high-risk NB patients have a dismal prognosis. Recent studies have underscored the pivotal role of neutrophil extracellular traps (NETs) in the proliferation, metastasis and immune evasion of cancer. To explore the effect of NETs on NB, we have carried out a systematic analysis and showed several findings in the present work. First, expression profiles along with clinical data were analyzed using the training dataset GSE62564 and 36 NETs-related genes were identified to be significantly associated with overall survival. Following LASSO regression analysis, 11 genes were enrolled to construct the NETs signature, which exhibited a robust predictive capability for overall survival with exhibiting high AUC values within the training set. Validation cohorts confirmed a similar predictive efficacy. Next, NB patients were classified into subgroups based on median risk scores and differentially expressed genes were analyzed. Furthermore, the study performed comprehensive analyses encompassing functional enrichment, immune infiltration and drug sensitivity. Enrichment analysis revealed that the high-risk NBs with high-risk score displayed characteristics of oncogenic malignancy, poor prognosis and immunosuppression. Notably, the risk score exhibited a strong correlation with infiltration levels of various immune cells and the sensitivity to anti-cancer drugs, and was further recognized as an independent prognostic factor for NB patients. In summary, our study elucidates a novel NETs-related gene signature comprising 11 genes, which serves a reliable predictor for NB prognosis.

Keywords

• Neuroblastoma
• Neutrophil extracellular traps
• Prognosis signature
• Therapeutic response
• Tumor immune microenvironment