PBMCs-Derived microRNA Signature as a Prethrombotic Status Discriminator in Stable Coronary Artery Disease

Prethrombotic status (PTS) in patients with stable coronary artery disease (SCAD) increases the risk of coronary thrombosis. Accumulating evidences have indicated that micro-ribonucleic acids (miRNAs) may serve as promising biomarkers for SCAD patients with PTS. The present study aimed to identify the miRNA signature in SCAD patients with PTS and evaluated their diagnostic significance. In the screening phase, 32 differently expressed miRNAs (DEMs) in peripheral blood mononuclear cells (PBMCs) were detected in 35 SCAD patients compared with 5 healthy controls by microarray. MiRNA-gene network analysis was then performed, and 4 DEMs were selected for validation with reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) test in an independent cohort comprising 79 SCAD patients and 19 healthy controls. Compared with healthy controls, RT-qPCR test verified the upregulations of miR-34a-5p, miR-432-5p, and miR-370-3p detected by microarray; while the upregulation of miR-495-3p measured by RT-qPCR was not consistent with its low expression detected by microarray. Only miR-34a-5p and miR-495-3p were significantly upregulated in the PTS group compared with the non-PTS group (p < 0.01, p < 0.05). Receiver-operating characteristic (ROC) analysis showed that PBMCs-derived miR-34a-5p and miR-495-3p may discriminate PTS with the areas under the ROC curve (AUC) of 0.780 (confidence interval [CI]_95% = 0.673-0.866) and 0.712 (CI_95% = 0.599-0.808), respectively. The combination of miR-34a-5p and fibrinogen (FIB, a traditional biomarker for PTS) improved AUC to 0.885 (CI_95% = 0.793-0.946) and showed added predictive ability compared with FIB, with an integrated discrimination improvement of 0.201 (p < 0.01). Therefore, the combination of miR-34a-5p and FIB may serve as an efficient tool for distinguishing PTS in SCAD patients.