AUTHOR=Wang Li , Zhang Jiting , Zhang Li , Hu Lingli , Tian Jianhui 

TITLE=Significant difference of differential expression pyroptosis-related genes and their correlations with infiltrated immune cells in sepsis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1005392

DOI=10.3389/fcimb.2022.1005392

ISSN=2235-2988

ABSTRACT=Background: Sepsis is regarded as a life-threatening organ dysfunctional syndrome that responded to infection. Pyroptosis, a unique form of programmed cell death, is characterized by inflammatory cytokines secretion. Recently, an increasing number of studies have investigated the relationship between sepsis and pyroptosis. Appropriate pyroptosis can help to control infection during sepsis, but immoderate one may cause immune disorders. The present study aimed to identify the pyroptosis-related gene biomarkers and their relationship with immune microenvironment using the genome-wide technique.
Methods: The training dataset GSE154918 and the validation dataset GSE185263 were downloaded for bioinformatics analysis. Differentially expressed pyroptosis-related genes (DEPRGs) were identified between sepsis (including septic shock) and healthy samples. Gene Set Enrichment Analysis (GSEA) was performed to explore gene function. CIBERSORT tools were applied to quantify infiltrating immune cells, and the correlation between differentially infiltrating immune cells and DEPRG expression was investigated. Besides, based on multivariable Cox regression, the study also utilized random forest model (RF) to screen biomarkers.
Results: 12 DEPRGs were identified. The expression level of PLCG1 was continuously significantly descended while the expression level of NLRC4 was elevated from control to sepsis then to septic shock. GSEA analysis found that one DEPRG (PLCG1) was involved in T cell receptor signaling pathway and many T cell-related immunologic signature gene sets were enriched. The proportions of plasma cells, T cells CD4 memory activated, and some innate cells in sepsis group were significantly higher than those in healthy group, while the proportions of T cells CD8, T cells CD4 memory resting, T cells regulatory (Tregs), and NK cells were lower. Additionally, CASP4 was positively correlated with Neutrophils and negatively correlated with T cells CD4 memory resting and Tregs. Lastly, two biomarkers (CASP4, PLCG1) were identified and a nomogram model was constructed for diagnosis with AUC values of 0.998.  
Conclusion: This study identified two potential pyroptosis-related diagnostic genes, CASP4 and PLCG1and explore the correlation between DEPRGs and immune microenvironment. Also, our study implicated that some DEPRGs were satisfactorily correlated with several representative immune cells that can regulate pyroptosis.