Identification of a ferroptosis-related gene signature for the prognosis of pediatric neuroblastoma

Background: Ferroptosis-related genes are correlated with the prognosis of patients with neuroblastoma (NB) remains unknown. This study aims to establish a prognostic ferroptosis-related gene model for predicting prognostic value in pediatric NB patients. Methods: The gene expression array and clinical characteristics of NB were downloaded from a public database. Correlations between ferroptosis-related genes and drug responses were analyzed by Childhood Cancer Therapeutics. The prognostic model was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression and was validated in NB patients from the ICGC cohort. The survival analysis was performed by Cox regression analysis. single-sample gene set enrichment analysis (ssGSEA) was used to quantify the immune cell infiltration correlation. Results: Overall, 70 genes were identified as ferroptosis-related differentially expressed genes (DEGs) from 247 samples. Then, 13 ferroptosis-related genes were correlated with OS in the univariate Cox regression analysis. Five prognostic ferroptosis-related DEGs (pFR-DEGs) (STEAP3, MAPDLC3A, ULK2, MTOR and TUBED), which were defined as the intersection of DEGs and prognostic ferroptosis-related genes, were identified and utilized to construct the prognostic signature. The correlation between five pFR-DEGs and drug responses was analyzed, and the box plots indicated that MTOR gene expression was highest, suggesting that MTOR expression is related to progressive NB disease. The receiver operating characteristic (ROC) curve showed that the model had moderate predictive power. The survival analysis indicated that the high- risk group had poor overall survival (OS) (P=2.087x10-06). Univariate and multivariate analyses identified the risk score as a significant prognostic risk factor [P=0.003, hazard ratio (HR) =1.933]. Immune cell infiltration correlation analysis showed that the high-risk group was related to more immune cells. Conclusions: The present study indicated a difference in ferroptosis-related gene expression between low- and high-risk NB patients. The ferroptosis-related signature could serve as a prognostic prediction tool. Additionally, immune infiltration might play an important role in different risk groups for NB patients.