Analysis and Validation of Autophagy Related Genes in Septic Acute Kidney Injury

Background: The pathogenesis of acute kidney injury (AKI) in sepsis involves inflammatory response. Autophagy has been shown to regulate inflammatory response, but the role of autophagy-related genes (ARGs) in the regulation of inflammation in septic AKI requires further investigation. Methods: Initially, the dataset GSE57065 was downloaded and utilized in the R language to investigate differentially expressed autophagy-related genes (DEARGs) associated with septic shock. Subsequently, DEARGs enrichment analysis and protein-protein interactions (PPIs) were conducted. Hub genes were identified through PPIs, and their diagnostic value was evaluated using ROC analyses with the external dataset GSE65682. Additionally, the septic AKI animal model was established to validate hub genes through qRT-PCR. Finally, immune cell infiltration in the septic AKI and control group was analyzed. Furthermore, we examined the correlation between immune cell infiltration and the validated hub genes, and predicted the miRNA-mRNA network. Results: In the GSE57065 dataset, we have identified 22 differentially expressed genes (DEGs) primarily involved in autophagy. The receiver operating characteristic (ROC) analysis suggested that the top ten hub genes may have diagnostic value. In our animal experiment, qRT-PCR results demonstrated elevated expressions of TP53, MYC, FOXO1, CXCR4, and BCL-2, while PARP1 and PTEN exhibited reduced expressions in septic AKI. The CIBERSORT analysis revealed immune infiltration, and the validated hub genes were associated with immune cell infiltration in septic AKI. Lastly, we have discovered potential regulatory miRNAs through the miRNA-mRNA network. Conclusions: The potential diagnostic and therapeutic targets, namely TP53, MYC, FOXO1, CXCR4, BCL-2, PARP1, and PTEN, have been identified as potentially influential factors in the infiltration of immune cells in acute kidney injury associated with sepsis.