A novel cuproptosis-related gene signature predicting overall survival in pediatric neuroblastoma patients

BACKGROUND: Cuproptosis is a novel cell death pathway, and the regulatory mechanism in pediatric neuroblastoma (NB) remains to be explored. We amid to investigate cuproptosis-related genes (CRGs) and construct a novel prognostic model for NB. METHODS: To evaluate the role of CRGs on the clinical outcome of pediatric NB, the dataset of pediatric patients with NB of GSE49710 dataset was used to identify CRGs in association with patient overall survival (OS), and TARGET database was used to validate the predictive value of cuproptosis-related signature (CRG-score). The correlation between the CRG-score and the tumor microenvironment (TME), clinicopathological parameters, chemotherapy, and the response to immunotherapy was explored. RESULTS: Overall, 31 CRGs were associated with OS in the univariate Cox regression analysis. Then, a prognostic model incorporating 9 CRGs was established with the LASSO regression analysis, which could classify all NB patients into two CRG-score groups. The performance of the signature was verified in both internal and external validation cohorts. Multivariate analysis indicated that the CRG-score was an independent prognostic indicator, and stratification analysis still showed a high predictive ability for survival prediction. The CRG-score was associated with age, MYCN status, INSS stage, and COG risk. Additionally, the higher CRG-score group exhibited lower immune scores, immune cell infiltration, and decreased expression of immune checkpoints. Meanwhile, the CRG-score could predict the drug sensitivity of administering chemotherapeutic agents for NB patients. CONCLUSIONS: Our comprehensive analysis of cuproptosis-associated genes in NB provides a new approach for the prediction of clinical outcomes and more effective treatment strategies.