Development Of An Individualized Immune Prognostic Signature Based On Neuroblastoma-immune Interaction

Purpose: Neuroblastoma(NBL)exists in a very complex immune microenvironment,and can form neoplastic lesions in any part of the spine.Regrettably,few researches has systematically discussed the immune-related molecular characteristics and prognostic potential of NBL.Methods: The whole genome sequencing data from 658 NBL samples were retrospectively analyzed.The ssGSEA and ssGSEA algorithms were used to analyze the immune cell infiltration,and the hierarchical clustering and t SNE algorithm were used to construct and verify the immune phenotype of NBL patients.The rank sum test was used to identify the differentially expressed immune genes between NBL patients with different immune phenotypes,and the prognostic potential of the differentially expressed immune genes was clarified through univariate Cox regression.A multivariate Cox risk regression model based on AIC was used to establish an individualized immune prognostic marker(IPGM)to predict the prognosis of NBL patients.The ROC curve,survival curve,correlation analysis,etc.have been used to verify the accuracy of the prognostic prediction of IPGM,and compared with the current common clinical prognostic characteristics.Univariate and multivariate Cox regression verified the independence of IPGM.Subsequently,the use of GO,KEGG enrichment analysis,PPI,correlation analysis,etc.clarified the construction of the multi-dimensional regulatory network of the key immune genes of IPGM.The multivariate Cox risk prognosis model is used to combine IPGM with clinical features to build a nomogram.Finally,the use of q RT-PCR,cell viability experiments,Ed U incorporation experiments,etc.,verified IPGM at the cell experiment.Results: Our study found that IPGM exhibited excellent individual risk stratification and prognostic potential(HR=3.49,p<0.001,AUC=0.819,cindex=0.718),MYCN status,chemokines and macrophage-related molecules,m6 A RNA methylation has a strong correlation with NBL-immune-related molecules.In addition,our comprehensive evaluation based on the combination of IPGM and clinical characterization showed better prognostic accuracy than simple clinical features.Conclusion: We systematically explored the NBL-immune-related molecular characteristics and constructed IPGM for the first time,which will bring new biological understanding to the deeper research of NBL and have clinical guidance value.