Identification of key genes and diagnostic biomarkers for peripheral atherosclerosis: A multi-omics approach.

Peripheral atherosclerosis (PAS), characterized by lipid plaque accumulation in arterial walls, significantly increases cardiovascular risk. This study aimed to identify molecular biomarkers and elucidate underlying mechanisms of PAS progression. We analyzed 2 gene expression omnibus datasets (GSE28829, GSE100927) to identify differentially expressed genes (P < .05, |log2FC| ≥ 0.585). Functional enrichment (Gene Ontology/Kyoto Encyclopedia of Genes and Genomes) and Mendelian randomization analyses were performed using genome-wide association study and expression quantitative trait loci data. Six hub genes were validated through single-cell RNA sequencing and independent datasets. A diagnostic nomogram was developed and evaluated using calibration curves, decision curve analysis, and receiver operating characteristic metrics. Integrated analysis revealed 6 key PAS-associated genes (leukocyte immunoglobulin-like receptor B1, hematopoietic cell-specific lyn substrate 1, plasminogen activator urokinase, C-type lectin domain family 2 member B, phosphatidylinositol-4-phosphate 5-kinase type 1 beta, cofilin 2). The diagnostic model demonstrated exceptional accuracy, achieving area under the receiver operating characteristic curves of 1.0 (training) and 0.975 (validation). Mendelian randomization confirmed causal relationships, with cofilin 2 and phosphatidylinositol-4-phosphate 5-kinase type 1 beta showing protective effects (odds ratio 0.74-0.90), while C-type lectin domain family 2 member B, hematopoietic cell-specific lyn substrate 1, leukocyte immunoglobulin-like receptor B1, and plasminogen activator urokinase emerged as risk factors. This multi-omics study identifies novel molecular signatures of PAS and establishes a robust diagnostic tool. The findings advance our understanding of PAS pathogenesis and pave the way for personalized therapeutic strategies.