Pyroptosis-Related Genes as Prognostic Biomarkers and Immune Infiltration Features in Sepsis-Induced ARDS: A Single-Cell and Bulk RNA-Sequencing Analysis

Pan Zhang,1,* Chun-Li Xu,2,* Li Xu,1 Jing Jing Wu,3 Li Wang4 1Department of Emergency, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 4Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Jing Wu, Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Email [email protected] Li Wang, Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Email [email protected]: Sepsis-induced acute respiratory distress syndrome (ARDS) is a common and costly syndrome with high mortality and poor prognosis without targeted therapies. Recently, pyroptosis has been demonstrated to be an inflammatory form of programmed cell death. However, the expression of pyroptosis-related genes (PRGs) in sepsis-induced ARDS and their correlation with prognosis remain unclear.Methods: In this study, 760 sepsis samples from public datasets were analyzed. We first conducted a comprehensive analysis of single-cell RNA-sequencing data of sepsis from the Gene Expression Omnibus database and identified 8 cell types and 38 hub genes. Subsequently, we used univariate Cox hazard analysis to narrow down the candidate genes and developed a prognostic model using the disease cohorts, which stratified patients into high- and low-risk groups. Four genes associated with the prognosis of patients with sepsis admitted to the intensive care unit for ≥ 28 days were identified.Results: High-risk patients have lower proportions of activated CD8+ T, effector memory CD8+ T, and memory B cells. The majority of the immune cells were positively correlated with each other. However, there was a negative association between neutrophils and other factors. Importantly, correlations between prognostic genes and the corresponding immune cells revealed that CCL5, CD3G, and IL7R were significantly associated with activated CD8+ T cells, and GIMAP4 was significantly negatively correlated with immune cells. Multivariate analysis identified the risk score as an independent prognostic factor.Conclusion: PRGs play a significant role in sepsis immunity. The above four key genes (CCL5, CD3G, IL7R, and GIMAP4) are expected to serve as clinical diagnostic targets, providing a basis for clinical prognosis stratification in patients with sepsis-induced ARDS and guiding the formulation of individualized treatment strategies.Keywords: sepsis, acute respiratory distress syndrome, pyroptosis-related genes, single-cell RNA-sequencing, prognosis