Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia

Abstract

Background Acute myelogenous leukemia (AML) is a common and fatal disease in hematology with frequent relapses and a poor prognosis. Pyroptosis, a programmed cell death mediated by inflammasomes, has been shown to be associated with leukemia recently. However, the role of pyroptosis for diagnosis and prognosis in AML remained less understood. Methods We downloaded three public datasets and constructed a signature of TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the overall survival of AML patients. Samples from the GEO database were treated as a validation cohort. Gone through LASSO-Cox regression analysis, an 8-PRG-related signature was developed. Used the median score from the signature, we classified patients in two subgroups. Subsequently, we employed univariate COX, multivariate Cox regression, ROC analysis and constructed a nomogram, Finally, differential analysis, GO and KEGG functional analysis, ESTIMATE algorithm and CIBERSORT algorithm were used to explore the difference between two groups. Results The expression levels of 90.9% pyroptosis-related genes (PRGs) had significant difference compared AML with normal tissues. The results of univariate COX regression analysis demonstrated 10 differentially expressed genes (DEGs) were associated with patients’ OS (p < 0.05). Then, we found OS of patients in the low-risk group was more likely to be lengthened compared with their high-risk counterparts (P < 0.05 both in the TCGA and GEO cohort). After controlling clinical factors, the risk score could still remain an independent predictive element (HR > 1, P < 0.001) of OS in multivariate Cox regression analysis. Furthermore, a nomogram with prognostic value for AML was thus established. Time-dependent ROC analysis proved the predictive power of the signature. Functional analysis suggested that DEGs were mainly concentrated in immune-related pathways, such as humoral immune response and T cell proliferation. TME scores and risk scores were strongly correlated and immune status differed between the risk subgroups. Conclusion A novel PRG-related signature was established to forecast the prognosis in AML, and pyroptosis may be a potential therapeutic target for AML.

Mechanisms of Erzhi Pill in Treating Lupus Nephritis Explored by GEO Gene Chips Combined with Network Pharmacology and Molecular Docking

“…28 CASP3 is an apoptotic factor that directly participates in the apoptosis of renal cells. 30 Studies have established the pivotal role of CASP3 for modulating renal fibrosis along with apoptosis of microvascular endothelial cells following ischemia-reperfusion injury. 31 Expression of caspase-3 within interstitial inflammatory cells, RTECs, and glomerular parenchymal cells have been reported to be higher in LN tissues compared with controls, suggesting the role of protein metabolism pathway in inducing apoptosis with regard to disease pathogenic mechanism, which has a certain effect on LN development via caspase-3 and MMP.…”

Development of a novel pyroptosis-related LncRNA signature with multiple significance in acute myeloid leukemia

“…The researches for the relationship between pyroptosis and tumor may provide some inspirations for clinical treatments. Recent several researches showed pyroptosis-related protein-coding genes could predict prognosis in AML ( He et al, 2022 ; Liu et al, 2022 ; Pan et al, 2022 ; Shao et al, 2022 ; Zhou et al, 2022 ).…”

A novel cuproptosis-related LncRNA signature: Prognostic and therapeutic value for acute myeloid leukemia

“…Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, which are classified as non-coding RNAs, and are involved in the epigenetic regulation of gene expressions (10). They are associated with distinct cell death types and are implicated in several cancer types, including AML (10)(11)(12)(13)(14)(15). Various lncRNAs are involved in leukemia and are potential diagnostic or prognostic biomarkers as well as therapeutic targets (16).…”