Front Immunol. 2026 Feb 2;17:1721069. doi: 10.3389/fimmu.2026.1721069. eCollection 2026.
ABSTRACT
BACKGROUND: Abdominal aortic aneurysm (AAA) is a severe vascular disease that can lead to rupture and life-threatening hemorrhage. The role of ferroptosis in AAA pathogenesis remains insufficiently understood. This study aims to investigate the role of ferroptosis in AAA by identifying ferroptosis-associated molecular subtypes and examining their relationship with immunological characteristics using an artificial neural network (ANN) model.
METHODS: We analyzed three publicly available datasets (GSE7084, GSE47472, and GSE57691) to identify differentially expressed ferroptosis-related genes (FRGs) and employed consensus clustering to classify AAA samples into two subtypes. Immune infiltration was assessed with the CIBERSORT algorithm, and a diagnostic artificial neural network (ANN) model based on subtype-specific genes was developed to discriminate ferroptosis-associated molecular subtypes and derive the NeuraAAA score.
RESULTS: Nine differentially expressed FRGs were identified, and the model incorporated three key genes (oncostatin M, heme oxygenase-1, and interleukin-6), achieving high diagnostic accuracy (AUC = 0.988). Consensus clustering stratified AAA samples into two ferroptosis-associated subtypes with distinct immune profiles, with the C1 subtype showing higher immune infiltration and immune scores than C2. The derived NeuraAAA score was elevated in the immune-enriched subtype and correlated with immune-cell infiltration, and a nomogram integrating NeuraAAA and immune score showed good calibration. Immunofluorescence confirmed increased expression of all three genes in AAA specimens.
CONCLUSION: Our study reveals the heterogeneous role of ferroptosis in AAA pathogenesis, demonstrating that ferroptosis-associated subtypes are linked to variations in the immune microenvironment. These findings provide new insights into AAA pathophysiology and suggest potential targets for subtype-specific therapeutic strategies, contributing to advances in precision medicine for AAA treatment.
PMID:41705251 | PMC:PMC12907547 | DOI:10.3389/fimmu.2026.1721069