Expression characteristics of ferroptosis-related immune genes in chronic pancreatitis and screening and validation of key genes.

OBJECTIVE: Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by persistent immune dysregulation and pancreatic injury. This study aimed to systematically investigate the expression characteristics of ferroptosis-related immune genes in CP and to identify key genes associated with disease status. METHODS: Two public transcriptomic datasets were analyzed to identify differentially expressed genes between CP and normal pancreatic tissues. Ferroptosis-related genes were obtained from the FerrDb database and intersected with differentially expressed genes. Functional enrichment, protein–protein interaction, and immune infiltration analyses were performed. A ferroptosis-related gene signature was constructed using LASSO regression and internally validated. A cerulein-induced CP mouse model was used for experimental validation by histological analysis and qRT-PCR. RESULTS: Nineteen ferroptosis-related differentially expressed genes were identified and enriched in oxidative stress–related pathways. Immune infiltration analysis suggested potential alterations in immune cell composition in CP; however, only plasma cells showed statistically significant differences between groups. The Ferro-Score model demonstrated excellent discrimination performance in the training dataset (AUC = 1.0). However, given that the model was evaluated only within the same dataset used for model construction, this result may reflect potential overfitting. Therefore, the predictive performance of the model should be interpreted with caution. The experimental verification at the mRNA level confirmed the differential expression of ZFP36 and BNIP3 in pancreatic tissue. CONCLUSION: This study identifies distinct ferroptosis-related immune gene signatures in CP and provides preliminary insights into the association between ferroptosis-related immune pathways and CP.