Diagnostic Value of Serum CXCL2 and Fibronectin-1 in Acute Myocardial Infarction and Their Association with Neutrophil Extracellular Trap Formation

Objective: Based on bioinformatics screening, C-X-C motif chemokine ligand 2 (CXCL2) and fibronectin 1 (FN1) were identified as common targets of acute myocardial infarction (AMI) and neutrophil extracellular traps (NETs). This study aimed to validate their adjunctive differential diagnostic value in emergency department patients with chest pain suspected of AMI, and explore NET associations. Methods: In this prospective observational study, 349 patients with chest pain suspected of AMI were enrolled between June 2022 and January 2025 and classified as non-AMI (n=226) or AMI (n=123). Serum CXCL2, FN1, and NETs biomarkers (myeloperoxidase-DNA [MPO-DNA] and citrullinated histone H3 [CitH3]) were measured by enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression, receiver operating characteristic (ROC) curves, and Spearman correlation were performed. Results: AMI patients had higher proportions of males, smokers, and angina, with elevated heart rate, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), and reduced high-density lipoprotein cholesterol (HDL-C) versus non-AMI ( P < 0.05). CXCL2, FN1, MPO-DNA, and CitH3 were elevated in AMI ( P < 0.05). Multivariable analysis showed heart rate, FBG, HbA1c, NLR, CXCL2, and FN1 as independent AMI factors, and HDL-C was negatively associated ( P < 0.05). ROC analysis showed AUCs of 0.786 and 0.755 for CXCL2 and FN1 alone, and 0.816 combined. CXCL2 and FN1 correlated positively with MPO-DNA and CitH3 ( P < 0.001). Conclusion: Serum CXCL2 and FN1 are elevated in AMI and correlate with NETs biomarkers. Combined detection demonstrated moderate diagnostic performance in patients with chest pain suspected of AMI, suggesting potential as novel auxiliary biomarkers for differential diagnosis in the ED. However, this single-center study had limited sample size and was positioned for differential diagnosis in symptomatic patients rather than asymptomatic screening. Multicenter, large-scale validation is needed to confirm reproducibility and generalizability, and functional studies (in vitro and in vivo) are required to clarify the mechanisms of NETs regulation.