Identification and validation of pyroptosis patterns in AML via comprehensive bioinformatics analysis

Abstract

Abstract Background Pyroptosis, a new type of programmed cell death, was associated with inflammation, immunity, and the development of tumor. However, the prognostic roles of pyroptosis-related genes and the correlation between pyroptosis and immunity in acute myeloid leukemia (AML) remains to be unrevealed. Methods This study analyzed the expression level and prognostic roles of 40 pyroptosis-related genes in AML patients. Clinical subtypes of AML were identified by nonnegative matrix factorization method (NMF) according to the expression level of pyroptosis-related genes. We also comprehensively explore the enrichment score (ES) of immunologic gene sets in different subtypes of AML by gene set variation analysis (GSVA). Least absolute shrinkage and selection operator method (LASSO) were used to seek prognostic immunologic gene sets and protein-protein interaction network was constructed to identify hub gens. Results 32 pyroptosis-related genes were differently expressed between AML and the healthy, and 9 pyroptosis-related genes were significantly associated with the prognosis of AML patients. We identified two clinically relevant subtypes of AML and patients with subtype 1 had a better overall survival. The ES of immunologic gene sets were significantly different in two subtypes of AML and four were associated with the prognosis of AML patients. Notably, MF enrichment and Reactome pathway indicated that four prognostic immunologic gene sets were mainly associated with terms of cell adhesion molecule binding, ubiquitin protein ligase binding, cytokine activity in MF, and interferon signaling, class I MHC mediated antigen processing & presentation. Finally, 9 hub genes were found from the four prognostic immunologic gene sets. Conclusions We demonstrated the important role of pyroptosis in AML and identified two AML subtypes. This provides additional useful data for the development of clinical therapy for AML.