Identification and Validation of Autophagy-Related Genes in Sepsis-Induced Acute Respiratory Distress Syndrome and Immune Infiltration

PURPOSE: Autophagy-related genes (ARGs) play an important role in the pathophysiology processes of sepsis-induced acute respiratory distress syndrome (ARDS). However, expression profiles of ARGs have rarely been used to explore the relationship between autophagy and sepsis-induced ARDS. Therefore, we aim to identify and validate the potential ARGs of sepsis-induced ARDS through bioinformatics analysis and experiment validation. METHODS: We downloaded GSE32707 data from the Gene Expression Omnibus (GEO) database. The potential differentially expressed genes (DEGs) and differentially expressed ARGs (DEARGs) of sepsis-induced ARDS were screened by R software. Then, we performed functional enrichment analyses to explore the potential biological functions of DEARGs and constructed protein–protein interaction (PPI) networks. Subsequently, correlation analysis and receiver operating characteristic (ROC) curve were used for the DEARGs. In addition, we estimated the proportions of 22 immune cell subsets by using CIBERSORT algorithm. Finally, RNA expression of seven DEARGs were validated by qRT-PCR in blood samples from sepsis-induced ARDS and healthy controls. RESULTS: We identified 28 DEARGs, including 11 up-regulated genes and 17 down-regulated genes, which were primarily involved in autophagy and apoptosis. Seven genes (BAG3, CTSD, ERBB2, MYC, PEA15, RAB24 and SIRT1) with AUC >0.70 were considered possible to be sepsis-induced ARDS hub genes for ROC curve analysis. CIBERSORT results shown that sepsis-induced ARDS contained a higher proportion of naive CD4(+) T cells, gamma delta T cells, monocytes, and neutrophils, and lower levels of CD8(+) T cells, memory resting CD4(+) T cells, follicular helper T cells were relatively lower. The results of qRT-PCR also demonstrated that the expression levels of BAG3, CTSD, ERBB2, MYC and SIRT1 in sepsis-induced ARDS patients and healthy controls had differences. CONCLUSION: We identified an association between DEGs and immune infiltration in sepsis-induced ARDS and validated BAG3, CTSD, ERBB2, MYC and SIRT1 that may be have excellent diagnostic performance.