Integrative analysis of multi-omics data for discovery of ferroptosis-related gene signature predicting immune activity in neuroblastoma

Immunotherapy for neuroblastoma remains unsatisfactory due to heterogeneity and weak immunogenicity. Exploring powerful signatures the evaluation of immunotherapy outcomes remain primary purpose. We constructed a ferroptosis-related gene (FRG) signature by least absolute shrinkage selection operator Cox regression, identified 10 independent prognostic FRGs in training cohort (GSE62564), then verified them an external validation (TCGA). Associated with clinical factors, accurately predicts overall survival 3, 5, years. An nomogram, which included FRG risk, age, stage International Neuroblastoma Staging System, MYCN status, was constructed. The area under curves showed satisfactory predicting performance. Through bulk RNA-seq proteomics data, we revealed relationship between hub genes key onco-promoter validated results MYCN-amplified MYCN–non-amplified cell lines qRT-PCR. significantly divided patients into high- low-risk groups, differentially expressed two groups were enriched immune actions, autophagy, carcinogenesis behaviors. group embodied higher positive component infiltration expression checkpoints more favorable cytolytic activity (CYT). predictive power this data from melanoma undergoing immunotherapy, satisfactory. Gene mutations closely related prognosis. AURKA PRKAA2 be nodal signature, both shown have different expressions INSS IV other stages after immunohistochemical validation. With single-cell analysis, found that T cells TNFA signaling interferon-γ hallmark. In conclusion, can predict work evaluating effects immunotherapy.