Prognostic implication of cuproptosis related genes associates with immunity in Ewing's sarcoma

Growing evidence demonstrated that cuproptosis play critical roles in human cancers. We aimed to identify the roles of cuproptosis related genes (CRGs) in prognosis and immunity of Ewing's sarcoma. The data of GSE17674 and GSE63156 were obtained from GEO. The expression of 17 CRGs and immune cells were explored, then correlation was analyzed. Based on CRGs, two molecular clusters were identified by consensus clustering algorithm. KM survival and IME features including immune cells, immune response, checkpoint genes between clusters were evaluated. NFE2L2, LIAS, and CDKN2A were screened out as prognostic signatures by univariate, LASSO and step regression. A risk model was established, and validated by KM method with p = 0.0026, and perfect AUC values. The accuracy of risk model was also well validated in external dataset. A nomogram was constructed and evaluated by calibration curves and DCA. Low level of immune cells, immune response, and enriched checkpoint genes were found in high-risk group. GSEA of signatures and GSVA of ES-related pathways revealed the potential molecular mechanism involved in ES progression. Several drugs showed sensitivity to ES samples. DEGs between risk groups were screened out, and function enrichment was conducted. Finally, scRNA analysis of GSE146221 was done. NFE2L2, and LIAS played crucial role in the evolution of ES by pesudotime and trajectory methods. Our study provided new aspects for further research in ES.