Abstract
Abdominal aortic aneurysm (AAA), a life-threatening cardiovascular disorder, necessitates the identification of novel molecular biomarkers to facilitate early diagnosis and precision therapeutic interventions. In this study, we employed an integrative bioinformatics strategy to systematically identify and characterise a potential biomarker for AAA. By reanalyzing GEO datasets and applying Lasso regression, we identified 10 candidate genes, whose intersection with known AAA-associated genes pinpointed LEF1 as a pivotal regulator. Single-cell transcriptomic analysis further demonstrated that LEF1 is predominantly expressed in aortic wall-resident T cells, suggesting a spatially restricted regulatory role. Functional enrichment analysis highlighted significant associations with MHC class II protein complex binding and ribosomal structural integrity, implicating LEF1 in immune and translational regulation. Immunohistochemical analysis demonstrated significantly elevated expression of CD3, CD4 and CD8 markers in AAA tissues compared to controls. Flow cytometry and immunofluorescence analyses confirmed LEF1 co-localisation with both CD8+ effector T cells and CD4+ memory T cells, with significantly enhanced LEF1 expression in AAA specimens versus controls. Overall, our study systematically discovered an important hub gene LEF1, which may serve as a biomarker for AAA.