Abstract
AML ranks second in the most common types of leukemia diagnosed in both adults and children. Necroptosis is a programmed inflammatory cell death form reported to be an innate immune effector against microbial and viral pathogens and recently has been found to play an eventful role in the oncogenesis, progression, and metastasis of cancer. This study is designed to explore the potential value of necroptosis in predicting prognostic and optimizing the current therapeutic strategies for AML patients. We collected transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases and selected necroptosis-related genes with both differential significance and prognostic value. Six genes (YBX3, ZBP1, CDC37, ALK, BRAF, and BNIP3) were incorporated to generate a risk model with the implementation of multivariate Cox regression. The signature was proven to be an independent prognostic predictor in both training and validation cohorts with hazard ratios (HRs) of 1.51 (95% CI: 1.33-1.72) and 1.57 (95% CI: 1.16-2.12), respectively. Moreover, receiver operating characteristic (ROC) curve was utilized to quantify the predictive performance of the signature and satisfying results were shown with the area under the curve (AUC) up to 0.801 (3-year) and 0.619 (3-year), respectively. In addition, the subtyping of AML patients based on the risk signature demonstrated a significant correlation with the immune cell infiltration and response to immunotherapy. Finally, we incorporated risk signature with the classical clinical features to establish a nomogram which may contribute to the improvement of clinical management. To conclude, this study identified a necroptosis-related signature as a novel biomarker to improve the risk stratification, to inform the immunotherapy efficacy, and to indicate the therapeutic option of targeted therapy.