cGAMP as a potential biomarker for diagnosing triple-vessel coronary artery disease in diabetic patients

Abstract Background Diabetes is closely associated with coronary artery disease (CAD), and diabetic patients are often in a state of chronic inflammation with immune dysfunction. Studies have shown that the systemic immune-inflammation index (SII) and high-sensitivity C-reactive protein (hs-CRP) are elevated in diabetic patients, reflecting the presence of chronic low-grade inflammation, which may play a critical role in the development and progression of cardiovascular diseases. However, early diagnosis of CAD in diabetic patients, especially in cases of triple-vessel disease, remains challenging. Purpose This study aims to explore cGAMP as a novel biomarker for diagnosing triple-vessel coronary artery disease in diabetic patients. We integrate basic research and clinical data to assess its potential in clinical diagnostics and explore its translational value as an early diagnostic tool. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from diabetic patients, and RNA sequencing (RNA-Seq) was performed to analyze gene expression profiles. KEGG pathway analysis revealed significant alterations in immune-related pathways, especially cytokine-cytokine receptor interactions and DNA sensing pathways, which may be closely associated with immune dysfunction and chronic inflammation. We then measured the serum levels of cGAMP and correlated them with the presence of triple-vessel coronary artery disease. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of cGAMP for CAD. Results RNA-Seq analysis revealed significant activation of immune-related signaling pathways, particularly cytokine signaling and DNA sensing pathways, providing a molecular basis for chronic inflammation in diabetes. Additionally, elevated cGAMP levels were strongly associated with the presence of triple-vessel coronary artery disease. ROC curve analysis showed that cGAMP achieved an area under the curve (AUC) of 0.71 (95% CI: 0.67-0.76), demonstrating moderate diagnostic performance. Conclusios cGAMP is a promising biomarker for diagnosing triple-vessel coronary artery disease in diabetic patients. With its moderate diagnostic accuracy, cGAMP has the potential to be translated into clinical practice as a non-invasive, easily accessible biomarker for early identification of high-risk diabetic patients, thus enabling early intervention. Future studies should focus on validating these findings in larger, multi-center cohorts and further exploring the clinical application of cGAMP in guiding treatment decisions, particularly in early screening and personalized treatment plans for coronary heart disease.Diabetes-Related Immune Changes and CAD