Analysis Of The Expression Profile Of Circular RNA In Coronary Heart Disease And Its Diagnostic Value

Background and objectiveCoronary artery disease?CAD?is a major cause of mortality and morbidity in the world,thus it's a serious threat to public health.Although there are effective treatments for CAD currently,the mortality rate remains high.One of the reasons for this discrepancy is the lack of highly sensitive and convenient diagnostic methods for CAD.In recent years,studies have shown that circular RNAs?circRNAs?are closely related to the occurrence and development of CAD and play roles of regulation in the pathology of CAD.The stability of circRNAs makes them become potential biomarkers for CAD,This study applied circRNA microarray chip to profile the circRNA expression patterns in peripheral blood mononuclear cells of CAD patients and healthy controls,screened differentially expressed circRNAs and evaluated the value of validated circRNAs as novel biomarkers for diagnosing CAD.Subjects and MethodsThe circRNA profiles of 24 CAD patients and 7 controls were performed by microarray.Fold-change ?1.5 and P value<0.05 were considered as the criteria for the selection of differentially expressed genes.TargetScan and miRanda were used to predict the binding of miRNA to circRNA.GO and KEGG were performed by using DAVID.Six classifiers were used to evaluate the optimal circRNA-signature for diagnosing CAD.The circRNA-signature and CAD-related circRNAs reported in previous studies were selected and replicated in a large independent cohort.Spearman correlation analysis were used to assess the relationship of validated circRNAs with cardiovascular risk factors and cardiac fimction parameters.Logistic regression analysis were performed to evaluate whether the validated circRNAs were independent impact factors for CAD occurrence.The ROC analysis was conducted to assess the diagnostic value of validated circRNAs.The expression levels of three circRNAs were detected in multiple human tissues and cell lines.ResultsIn the circRNA microarray,there were 624 circRNAs significantly upregulated and 171 circRNAs significantly downregulated in CAD patients compared to healthy controls.The classifiers verified a nine-circRNA signature that can be used to diagnose CAD,including hsa_circ₀01879,hsa_circ₀066609,hsa_circ₀073402,hsa_circ₀091846,hsa_circ₀078625,hsa_circ 0066608,hsa_circ₀04104,hsa_circ₀04432 and hsa_circ₀07142.Previous studies showed that circTCF25,hsa_circ₀05075 and hsa_circ₁569 might be related to CAD.In the validation cohort,the expression levels of hsa_circ₀01879 and hsa_circ₀04104 were significantly upregulated in the cases?P<0.05?,and circTCF25 significantly downregulated?P<0.05?when compared to controls.Logistic regression analysis showed that with a unit increments of hsa_circ₀01879,hsa_circ₀04104 and circTCF25,the adjusted ORs for CAD occurrence were 1.58?95%CI:1.29-1.93,P<0.001?,2.53?95%CI:1.68-3.81,P<0.001?and 0.55?95%CI:0.39-0.77,P<0.001?,respectively.The area under the ROC curve of hsa_circ₀01879,hsa_circ₀04104 and circTCF25 was 0.70?95%CI:0.66-0.75,P<0.001?,0.70?95%Cl:0.65-0.76,P<0.001?and 0.62?95%CI:0.57-0.67,P<0.001?,respectively.The expression levels of there circRNAs were high in CVD-related cell lines and circTCF25 was high in CVD-related tissues.ConclusionIn this study,we offered a transcriptome-wide overview of aberrantly expressed circRNAs in CAD patients,and hsa_circ₀01879 and hsa_circ₀04104 were significantly upregulated and circTCF25 was significantly downregulated in CAD patients,which could be used as novel biomarkers for diagnosing CAD.Our findings provide new ideas for CAD diagnosis and treatment.