Comprehensive analysis of the ability of the Cuproptosis- related gene signature to predict the prognosis of patients with pediatric acute myeloid leukemia

Abstract Background: Cuproptosis is a new type of Regulated Cell Death (RCD) that is distinct from other known types of cell death, and novel prognostic models for leukemia have been proposed based on this process. However, most studies have been performed predominantly in adults. The potential roles of cuproptosis in pediatric leukemia remain unclear. Methods: We comprehensively analyzed the expression and mutation sites of CRGs in both pediatric and adult AML patients. Least absolute shrinkage and selection operator (LASSO) was used to construct a cuproptosis-related signature, and univariate Cox regression and differential gene analysis were also performed. According to the risk model, AML patients were divided into two groups. Several statistical approaches, such as Kaplan‒Meier, receiver operating characteristic (ROC), Cox regression, and calibration curve analyses, were used to evaluate the prognostic value of the model. Furthermore, the associations between risk group and immune cell infiltration, HLA expression, immune checkpoint expression, and therapeutic drug sensitivity were also analyzed. Finally, the expression of the mRNAs in the signatures was investigated in AML clinical samples by quantitative polymerase chain reaction (qPCR) to demonstrate the reliability of our analysis. Results: Our results revealed differences in the expression levels and prognostic value of CRGs between adult and pediatric AML patients. Subsequently, four CRG signatures (FAU, RPL19, TRAIP, and TEFM) were generated. Cox regression analyses demonstrated that the signature was an independent predictor of prognosis. GO and KEGG analyses also revealed that the signature was significantly associated with memory T-cell activation and negatively correlated with natural killer (NK) and regulatory T-cell activation. In addition, we identified the distinctive agents neopeltolide, gemcitabine, oligomycin A, ect. weresensitive to high-risk pediatric AML patients. Finally, we used clinical samples to validate the expression and prognostic value of the four CRG signatures to verify the results. Conclusions: Our observations revealed disparate functions of CRGs in pediatric and adult AML patients. A cuproptosis-related signature was established to predict patient prognosis and inform potential therapeutic strategies for pediatric AML patients. As the first attempt to determine pediatric AML prognosis using RCD biomarkers, we provide new insight into the prognosis assessment field.