Clinical significance of circulating microRNAs as diagnostic biomarkers for coronary artery disease

Abstract

Coronary artery disease (CAD) is one of the biggest threats to human life. Circulating microRNAs (miRNAs) have been reported to be linked to the pathogenesis of CAD, indicating the possible role in CAD diagnosis. The present study aimed to explore the expression profile of plasma miRNAs and estimate their value in diagnosis for CAD. 67 Non-CAD control subjects and 88 CAD patients were enrolled. We conducted careful evaluation by RT-PCR analysis, Spearman rank correlation coefficients analysis, Receiver Operating Characteristic (ROC) curves analysis and so on. The plasma levels of six miRNAs known to be related to CAD were measured and three of them showed obvious expression change. Circulating miR-29a-3p, miR-574-3p and miR-574-5p were all significantly increased. ROC analysis revealed the probability of the three miRNAs as biomarkers with AUCs (areas under the ROC curve) of 0.830, 0.792 and 0.789, respectively. They were significantly correlated with each other in CAD patients, suggesting the possibility of joint diagnosis. The combined AUC was 0.915, much higher than each single miRNA. Therefore, our study revealed three promising biomarkers for early diagnosis of CAD. The combination of these miRNAs may act more effectively than individual ones for CAD diagnosis.

Keywords: circulating micrornas; combined diagnosis; coronary artery disease; diagnostic biomarkers.

Figure 1

Clinical characteristics of the study population and plasma levels of circulating miRNAs. A, Baseline and clinical characteristics of the study population. BMI, body mass index; CK‐MB, creatine kinase‐MB; HDL, high‐density lipoprotein; hsTnT, high‐sensitivity troponin T; LDL, low‐density lipoprotein; MYO, myoglobin; NT‐proBNP, N‐terminal pro–B‐type natriuretic peptide; TC, total cholesterol; TG, total triglyceride; WBC, white blood cell. Data are shown as mean ± SEM; *P < .05 and **P < .01. B, Plasma levels of miR‐29a‐3p. C, Plasma levels of miR‐134‐3p. D, Plasma levels of miR‐223‐3p. E, Plasma levels of miR‐574‐3p. F, Plasma levels of miR‐574‐5p. G, Plasma levels of miR‐765. Expression levels of selected miRNAs were analysed by qRT‐PCR, and U6 snRNA was used as the reference gene. Data are presented as mean ± SEM

Figure 2

Correlation analysis and diagnostic value analysis. A, Correlation of miR‐29a‐3p and miR‐574‐3p in CAD patients. B, Correlation of miR‐29a‐3p and miR‐574‐5p in CAD patients. C, Correlation of miR‐574‐3p and miR‐574‐5p in CAD patients. D, Correlation of CK‐MB and miR‐574‐3p. E, Correlation of CK‐MB and miR‐574‐5p. F, ROC curve of miR‐29a‐3p, control patients vs. CAD patients. G, ROC curve of miR‐574‐3p, control patients vs. CAD patients. H, ROC curve of miR‐574‐5p, control patients vs. CAD patients. I, Diagnostic value analysis of circulating miRNAs by ROC curve. The figures depict calculated ROC curve of three circulating miRNAs and the combined ROC curve