Ferroptosis-Related Genes Are Effective Markers for Diagnostic Targets of Crohn's Disease

Crohn's disease (CD) is a group of chronic transmural inflammation of gastrointestinal tract, which seriously harms the mental and physical health of adolescents. At present, there are still no specific markers that make the diagnosis of CD extremely difficult and poor prognosis. Iron deficiency is common in CD, yet the role of ferroptosis-related genes in CD has not been elucidated.

The serum iron and ferritin levels were detected in 107 newly diagnosed CD patients and 107 healthy volunteers in our hospital. Bioinformatics analysis was used to analyze the chip sequencing data of CD in GEO database. Immunohistochemical analysis of paired inflammatory and noninflammatory intestinal tissues from CD patients was performed to confirm the differential protein expression pattern of the target genes.

Patients with CD exhibited significantly reduced serum iron and ferritin levels compared to healthy controls. Transcriptomic analysis identified 40 upregulated and 31 downregulated ferroptosis-associated genes in CD patients versus controls. LASSO regression and SVM-RFE algorithms prioritized 13 hub genes (e.g., CDKN2A, LCN2, STAT3, MT1G), with a ROC curve demonstrating 100% specificity for combined biomarker analysis. Despite robust bioinformatic predictions, serum RNA levels of CDKN2A, LIG3, and MTF1 showed no intergroup differences. Immuno-reactivity score validated protein expression consistency for LCN2, PANX1, LPIN1, PML, STAT3, PARP9, RELA, NEDD4, and MT1G but not PPARD or LCN2. Expression patterns of these genes correlated with M0 macrophage infiltration, resting mast cells, and neutrophil recruitment, suggesting immune-microenvironment interactions in CD progression.

Combined detection of ferroptosis-related genes is of great value in the diagnosis of CD.