Identification of pyroptosis-related immune signature and drugs for ischemic stroke

Abstract

Background: Ischemic stroke (IS) is a common and serious neurological disease, and multiple pathways of cell apoptosis are implicated in its pathogenesis. Recently, extensive studies have indicated that pyroptosis is involved in various diseases, especially cerebrovascular diseases. However, the exact mechanism of interaction between pyroptosis and IS is scarcely understood. Thus, we aimed to investigate the impact of pyroptosis on IS-mediated systemic inflammation.Methods: First, the RNA regulation patterns mediated by 33 pyroptosis-related genes identified in 20 IS samples and 20 matched-control samples were systematically evaluated. Second, a series of bioinformatics algorithms were used to investigate the contribution of PRGs to IS pathogenesis. We determined three composition classifiers of PRGs which potentially distinguished healthy samples from IS samples according to the risk score using single-variable logistic regression, LASSO-Cox regression, and multivariable logistic regression analyses. Third, 20 IS patients were classified by unsupervised consistent cluster analysis in relation to pyroptosis. The association between pyroptosis and systemic inflammation characteristics was explored, which was inclusive of immune reaction gene sets, infiltrating immunocytes and human leukocyte antigen genes.Results: We identified that AIM2, SCAF11, and TNF can regulate immuno-inflammatory responses after strokes via the production of inflammatory factors and activation of the immune cells. Meanwhile, we identified distinct expression patterns mediated by pyroptosis and revealed their immune characteristics, differentially expressed genes, signaling pathways, and target drugs.Conclusion: Our findings lay a foundation for further research on pyroptosis and IS systemic inflammation, to improve IS prognosis and its responses to immunotherapy.

Machine Learning Analysis of Gene Expression Profiles ofPyroptosis-Related Differentially Expressed Genes in IschemicStroke Revealed Potential Targets for Drug Repurposing

“…Pyroptosis plays an essential role in mediating cell death and clinical prognosis of various neurological disorders such as central nervous system infections, autoimmune disorders, neurodegenerative diseases, traumatic brain and spinal cord injuries, cerebral hemorrhagic and IS [16][17][18][19]. Recently, an increasing number of studies have been conducted to search for pyroptosis-related biomarkers as potential indicators for predicting the development of disease and therapeutic target of drug discovery [20].…”

N6-methyladenosine modulation classes and immune microenvironment regulation in ischemic stroke

“…Another study developed diagnostic model for acute IS based on four circulating microRNAs (miR-125a-5p, miR-125b-5p, and miR-143-3p; Tiedt et al, 2017 ). Moreover, another pyroptosis-related immune model had been constructed for IS prognosis and its responses to immunotherapy ( Shi et al, 2022 ). The pathophysiological processes following stroke are complex and extensive, and the inflammatory response plays a key role in the pathophysiological processes following ischemic stroke ( Fu et al, 2015 ).…”