NPM1 Promises To Be A Novel Therapeutic Target And Prognostic Biomarker For Ewing Sarcoma

Objective Ewing’s sarcoma（ES）is a cancer that may originate from stem cell mesenchymal or neural crest cells and is very prevalent in children and adolescents.In recent years,targeted therapies against immune-related genes have shown promising efficacy in a variety of cancers.However,effective targets for ES immunotherapy have not been developed.We hope to develop new ES therapeutic targets through bioinformatics combined with molecular biology experiments.MethodsUsing single-sample gene set enrichment analysis（ss GSEA）with co-expression network analysis（WGCNA）by GEO dataset GSE34620 with GSE17674,we first identified immune-associated differential genes in ES and screened the core genes by protein interaction network（PPI）.Then,the biological function of the gene was verified using various experimental methods such as real-time quantitative-PCR,western blot,and flowmetry apoptosis,and finally,the impact of the gene expression on the survival of ES patients was explored.ResultsThrough bioinformatics analysis,we identified 85 immune infiltration negatively associated differential genes in ES.The NPM1 inhibitor NSC348884 can inhibit ES cell proliferation and induce apoptosis in a dose-dependent manner,and is expected to be a potential therapeutic agent for ES.ConclusionIn conclusion,our study found that NPM1 can interact with MYC,CCND1,WNT5 A and HISTIH2 BH to affect the development and progression of ES.While targeting NPM1 not only promotes apoptosis and inhibits ES cell proliferation but also serves as an immunotherapeutic target to reactivate immune infiltration in ES patients.the NPM1 inhibitor NSC348884 induces apoptosis in a dose-dependent manner and is expected to be a novel therapeutic agent for ES.