Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris

Chunjian Li, Zhijuan Fang, Ting Jiang, Qiu Zhang, Chao Liu, Chenyu Zhang, Yang Xiang, Chunjian Li, Zhijuan Fang, Ting Jiang, Qiu Zhang, Chao Liu, Chenyu Zhang, Yang Xiang

Abstract

Background: In order to identify miRNAs expression profiling from genome-wide screen for diagnosis of acute myocardial infarction (AMI) and angina pectoris (AP), we investigated the altered profile of serum microRNAs in AMI and AP patients at a relative early stage.

Methods: Serum samples were taken from 117 AMI patients, 182 AP patients and 100 age-and gender-matched controls. An initial screening of miRNAs expression was performed by Solexa sequencing. Differential expression was validated using RT-qPCR in individuals samples, the samples were arranged in a two-phase selection and validation.

Results: The Solexa sequencing results demonstrated marked upregulation of serum miRNAs in AMI patients compared with controls. RT-qPCR analysis identified a profile of six serum miRNAs (miR-1, miR-134, miR-186, miR-208, miR-223 and miR-499) as AMI biomarkers. MiR-208 and miR-499 were elevated higher in AP cases than in AMI cases. The ROC curves indicated a panel of six miRNAs has a great potential to offer sensitive and specific diagnostic tests for AMI. More especially, the panel of six miRNAs presents significantly differences between the AMI and AP cases.

Conclusions: The six-miRNAs signature identified from genome-wide serum miRNA expression profiling may serves as a fingerprint for AMI and AP diagnosis.

Figures

Figure 1
Figure 1
Flow chart of the experimental design.
Figure 2
Figure 2
MiRNAs levels in AMI patients and control samples in the training set. Serum levels of the six miRNAs were measured in 20 AMI and 20 healthy control subjects using a hydrolysis probe-based RT-qPCR assay. (*P<0.05, **P<0.01, ***P<0.001).
Figure 3
Figure 3
MiRNAs levels in AMI patients and control subjects in the validation set. Serum levels of the six miRNAs were measured in 97 AMI and 80 healthy control subjects using a hydrolysis probe-based RT-qPCR assay. (*P<0.05, **P<0.01, ***P<0.001).
Figure 4
Figure 4
MiRNAs expression in AMI patients, AP patients and control subjects. Serum levels of the six miRNAs were measured in 117 AMI cases, 182 AP cases and 100 healthy control subjects using a hydrolysis probe-based RT-qPCR assay (A-F). (*P<0.05, **P<0.01, ***P<0.001).
Figure 5
Figure 5
ROC curves constructed to compare the relative concentrations of the 6 miRNAs. ROC curves for the 6-miRNAs panel, cTnT and CK-MB to differentiate AMI cases from the controls(A-C); ROC curves for the 6-miRNAs panel, cTnT and CK-MB (D-F) to differentiate AP cases from the controls; ROC curves for the 6-miRNAs panel , cTnT and CK-MB (G-I) to differentiate AMI cases from AP cases.

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