Elevated CD56 (NCAM1) expression is associated with immune activation and disease severity in atherosclerosis: clinical and transcriptomic validation study

Purpose: Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation within the arterial wall and immune dysregulation. Reliable immune-related biomarkers for early diagnosis and disease severity assessment remain limited. This study aimed to investigate the association between CD56 (NCAM1) gene expression and atherosclerotic disease, evaluate its relationship with disease severity, and validate the findings using an independent transcriptomic dataset.Materials and Methods: The study included 96 participants, comprising 48 patients with angiographically confirmed atherosclerosis and 48 healthy controls. We quantified peripheral blood CD56 (NCAM1) gene expression by quantitative real-time PCR, using GAPDH as the reference gene. We evaluated associations between CD56 expression, clinical characteristics, and SYNTAX scores. We performed receiver operating characteristic (ROC) curve analysis and multivariate logistic regression to assess diagnostic performance and the independent association of CD56 expression with atherosclerosis. We conducted transcriptomic validation using a publicly available coronary artery disease dataset, followed by immune enrichment analysis.Results: CD56 (NCAM1) expression was markedly higher in patients with atherosclerosis than in healthy controls (median [IQR]: 5.24 [2.77–23.77] vs. 0.79 [0.45–1.92]). ROC analysis demonstrated strong diagnostic performance, with an AUC of 0.882, a sensitivity of 87.5%, and a specificity of 75.0%. Multivariate logistic regression identified CD56 expression as an independent predictor of atherosclerosis (OR = 1.187, 95% CI: 1.060–1.330). CD56 expression was also strongly and positively correlated with SYNTAX scores (Spearman's ρ = 0.767). Transcriptomic analysis confirmed elevated NCAM1 expression in coronary artery disease samples and revealed enrichment of NK cell-related immune signatures, supporting the clinical findings.Conclusion: Elevated CD56 (NCAM1) expression is associated with both the presence and severity of atherosclerotic disease and reflects enhanced immune activation. The concordance between clinical and transcriptomic analyses suggests that CD56 may serve as a promising biomarker for the diagnosis and risk stratification of atherosclerosis. Further large-scale prospective studies are warranted to validate its clinical applicability.