Identification and validation of ferroptosis-associated genes in pancreatic and liver tissues for acute pancreatitis and their impact on immune infiltration

Acute pancreatitis is a systemic inflammatory response that has the potential to affect numerous organs, resulting in persistent multiorgan failure and necrosis of the pancreas. According to previous studies, the development and occurrence of acute pancreatitis are linked to ferroptosis and immune responses. We assessed and validated the function of ferroptosis-related genes in acute pancreatitis and their association with inferred immune infiltration using bioinformatic analyses. Ferroptosis-related differentially expressed genes were identified using the Gene Expression Omnibus databases (GSE109227, GSE121038, and GSE183158) in conjunction with our transcriptome sequencing data. The involvement of ferroptosis-related differentially expressed genes was clarified through gene ontology, differential gene correlation, and gene set enrichment analysis. CIBERSORT analysis was used to evaluate and internally validate the immune microenvironment in acute pancreatitis. Comparative analysis of sequencing data from the pancreatic and liver tissues revealed 13 ferroptosis-related differentially expressed genes in acute pancreatitis. Gene ontology analysis primarily identified enrichment for iron ions, protein phosphatase, and actin filament binding. Gene set enrichment analysis predominantly highlighted the interleukin-18 and interleukin-23 pathways. Hub genes in the protein-protein interaction network included Egfr, Fads1, Hsp90b1, Krt18, Lcn2, Myh9, Pdia6, and Sqle. We identified 80 miRNAs, 67 transcription factors, and 24 potential drugs or molecular compounds associated with acute pancreatitis pathology. Quantitative reverse transcription polymerase chain reaction performed on caerulein-induced acute pancreatitis mouse models confirmed significant downregulation of Fads1, Hsp90b1, Pdia6, Sqle, and Cisd1 mRNA levels while showing significant upregulation of Osbpl9, Myh9, and Zfp36 mRNA levels. These findings suggested that these genes may represent candidate genes associated with AP and ferroptosis. Thirteen ferroptosis-related differentially expressed genes were discovered within the framework of acute pancreatitis, and their association with immune cell infiltration was studied. Future investigations should explore the possibility of Fads1, Hsp90b1, Pdia6, Sqle, Cisd1, Osbpl9, Myh9, and Zfp36 as novel therapeutic targets.