Abstract

The aim of the present study was to investigate the expression of circular RNAs (circRNAs) in the peripheral blood of coronary artery disease (CAD) patients and the potential use of circRNAs as diagnostic biomarkers of CAD. We first analysed peripheral blood circRNAs of 12 CAD patients and 12 control individuals by RNA microarray and found that 22 circRNAs were differentially expressed between these two groups: 12 were upregulated, and 10 were downregulated. Then, we selected 5 circRNAs as candidate biomarkers under stricter screening criteria and verified them in another group of subjects consisting of 30 control individuals and 30 CAD patients with different SYNTAX scores. These 5 circRNAs were all remarkably increased in the CAD group. Hsa_circ_0124644 had the largest area under the curve (AUC). We tested hsa_circ_0124644 in an independent cohort consisting of 115 control individuals and 137 CAD patients. After we included the risk factors for CAD, the AUC slightly increased from 0.769 (95% confidence interval = [0.710–0.827], P < 0.001) to 0.804 ([0.751–0.857], P < 0.001), and when combined with hsa_circ_0098964, the diagnostic value slightly increased. Taken together, our results suggest that hsa_circ_0124644 can be used as a diagnostic biomarker of CAD.

Highlights

  • According to a 2014 statistical summary by the World Health Organization (WHO), cardiovascular diseases are the most lethal non-communicable diseases (NCD), accounting for 46% of all NCD mortality

  • Subjects were excluded according to the following criteria: 1) malignancies; 2) liver and kidney dysfunction; 3) any other clinically systemic acute or chronic inflammatory diseases; 4) history of acute myocardial infarction (AMI), percutaneous coronary intervention (PCI), or coronary artery bypass graft surgery (CABG); 5) autoimmune disease; 6) uncontrolled hypertension; or 7) malignant arrhythmias or valvular heart disease

  • To identify whether circRNAs are differentially expressed between coronary artery disease (CAD) patients and normal subjects, we extracted peripheral blood total RNA from 12 CAD patients and 12 controls for circRNA microarray assay analysis

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Summary

Introduction

According to a 2014 statistical summary by the World Health Organization (WHO), cardiovascular diseases are the most lethal non-communicable diseases (NCD), accounting for 46% of all NCD mortality. Despite the current standardized treatments of CAD, which include medications, percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG), the prognosis remains unsatisfactory in some patients[2,3]. This discrepancy is mainly because the current diagnostic methods cannot simultaneously achieve high sensitivity and convenience, which obviously increases the missed diagnosis rate. Li et al.[19] found that the expression of hsa_circ_002059 in gastric cancer tissue is significantly higher compared with that in adjacent tissues; this circRNA is used in the clinic as a novel biomarker of gastric cancer. Our results indicated that hsa_circ_0124644 may be a sensitive and specific biomarker for diagnosing CAD

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