ArticleFrontiers in immunology2026
Disulfidptosis-related genes define a prognostic signature and novel therapeutic targets in Ewing's sarcoma through transcriptomic analysis and experimental validation.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Ewing's sarcoma (ES) is a malignant osseous neoplasm characterized by a dismal prognosis, particularly in its metastatic variant. The significance of disulfidptosis-a newly identified cell death mechanism induced by cystine metabolic imbalance and mitochondrial dysfunction-has yet to be investigated in ES. Thus, the aim of this study was to assess the prognostic significance of disulfidptosis-related genes (DRGs) in this disease. Methods: We analyzed four GEO datasets to examine nine DRGs through differential expression, co-expression networks, and functional enrichment analyses. A predictive risk signature was developed using unsupervised clustering, Cox regression, and LASSO. Drug sensitivity was predicted using the GDSC database, and immune infiltration was quantified by ssGSEA. Single-cell RNA sequencing data was analyzed to explore DRGs distribution and functional heterogeneity. Molecular docking simulations were performed to evaluate interactions between DRGs and chemotherapeutic agents. Experimental validation of key DRGs was conducted in RD-ES cells using PCR and Western blotting, followed by functional studies of Results: Eight of nine DRGs were dysregulated in ES tissues. A five-gene risk model ( Conclusion: This study provides the first prognostic signature connected to disulfidptosis for ES. Functional validation of
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