MiRNAs as biomarkers of myocardial infarction: a meta-analysis

Abstract

Background: Recent studies have demonstrated that acute myocardial infarction induces a distinctive miRNA signature, suggesting that miRNAs may serve as diagnostic markers. Although many studies have investigated the use of miRNAs in the detection of cardiac injury, some had small sample sizes (<100 patients) or reported different results for the same miRNA. Here, the role of circulating miRNAs for use as biomarkers of myocardial infarction is summarized and analyzed.

Methods and results: Medline, SCI, Embase, and Cochrane databases were searched up to January 2013 for studies that evaluated associations between miRNAs and myocardial infarction. Relevant publications were identified by searching for combinations of "myocardial infarction," "miRNAs," and their synonyms. Methodological quality was scored using a standardized list of criteria, and diagnostic performance was assessed using estimates of test sensitivity and specificity. These values were summarized using summary receiver-operating characteristic curves. Nineteen studies met the inclusion criteria: 15 studies reported sensitivity, specificity, and AUC, but 4 studies did not. Total miRNAs: sensitivity: 0.78 (95%CI: 0.77-0.80; P = 0.0000); specificity: 0.82 (95%CI: 0.80-0.83; P = 0.0000). miR-499: sensitivity: 0.88 (95%CI:0.86-0.90; P = 0.0000); specificity: 0.87 (95%CI:0.84-0.90; P = 0.0000). miR-1: sensitivity: 0.63 (95%CI:0.59-0.66; P = 0.0000); specificity: 0.76 (95%CI:0.71-0.80; P = 0.0000). miR-133a: sensitivity: 0.89 (95%CI:0.83-0.94; P = 0.0047); specificity: 0.87 (95%CI:0.79-0.92; P = 0.0262). miR-208b: sensitivity: 0.78 (95%CI:0.76-0.81; P = 0.0581); specificity: 0.88 (95%CI:0.84-0.91; P = 0.0000). The correlation between miRNAs and other diagnostic biomarkers of myocardial infarction was obvious.

Conclusion: MiRNAs, especially miR-499 and miR-133a, may be suitable for use as diagnostic biomarkers of myocardial infarction.

Figure 1. Flow diagram of the literature search and study selection.

Figure 2. The sensitivity, specificity, diagnostic OR, SROC curve with AUC and funnel plot for total miRNA levels of 15 studies in the diagnosis of myocardial infarction.

(A) Sensitivity. (B) Specificity. (C) Diagnostic OR. (D) SROC curve with AUC. (E) Funnel plot. Df, degree of freedom; OR, odds ratio; SROC, summary receiver operator characteristics; AUC, area under the curve; SE, standard error; Q*, Q index. Balls, estimated respectively the sensitivity, specificity, diagnostic OR, AUC; Bars, 95% confidence intervals (CIs); Width of diamonds, pooled CIs. The size of each ball is proportional to the weight of each study in the meta-analysis. The SROC show all values of AUC and the area between the upper left and lower right curves represent the CIs of AUC for total miRNA levels. Values that cross the borders are not shown in these figures. Boxes in the funnel plot indicated the studies included in this meta- analysis.

Figure 3. The sensitivity, specificity, diagnostic OR, SROC curve with AUC and funnel plot for miR-499 levels of 8 studies in the diagnosis of myocardial infarction.

(A) Sensitivity. (B) Specificity. (C) Diagnostic OR. (D) SROC curve with AUC. (E) Funnel plot. Df, degree of freedom; OR, odds ratio; SROC, summary receiver operator characteristics; AUC, area under the curve; SE, standard error; Q*, Q index. Balls, estimated respectively the sensitivity, specificity, diagnostic OR, AUC; Bars, 95% confidence intervals (CIs); Width of diamonds, pooled CIs. The size of each ball is proportional to the weight of each study in the meta-analysis. The SROC show all values of AUC and the area between the upper left and lower right curves represent the CIs of AUC for total miRNA levels. Values that cross the borders are not shown in these figures. Boxes in the funnel plot indicated the studies included in this meta- analysis.

Figure 4. The sensitivity, specificity, diagnostic OR, SROC curve with AUC and funnel plot for miR-1 levels of 7 studies in the diagnosis of myocardial infarction.

(A) Sensitivity. (B) Specificity. (C) Diagnostic OR. (D) SROC curve with AUC. (E) Funnel plot. Df, degree of freedom; OR, odds ratio; SROC, summary receiver operator characteristics; AUC, area under the curve; SE, standard error; Q*, Q index. Balls, estimated respectively the sensitivity, specificity, diagnostic OR, AUC; Bars, 95% confidence intervals (CIs); Width of diamonds, pooled CIs. The size of each ball is proportional to the weight of each study in the meta-analysis. The SROC show all values of AUC and the area between the upper left and lower right curves represent the CIs of AUC for total miRNA levels. Values that cross the borders are not shown in these figures. Boxes in the funnel plot indicated the studies included in this meta- analysis.

Figure 5. The sensitivity, specificity, diagnostic OR, SROC curve with AUC and funnel plot for miR-133a levels of 4 studies in the diagnosis of myocardial infarction.

(A) Sensitivity. (B) Specificity. (C) Diagnostic OR. (D) SROC curve with AUC. (E) Funnel plot. Df, degree of freedom; OR, odds ratio; SROC, summary receiver operator characteristics; AUC, area under the curve; SE, standard error; Q*, Q index. Balls, estimated respectively the sensitivity, specificity, diagnostic OR, AUC; Bars, 95% confidence intervals (CIs); Width of diamonds, pooled CIs. The size of each ball is proportional to the weight of each study in the meta-analysis. The SROC show all values of AUC and the area between the upper left and lower right curves represent the CIs of AUC for total miRNA levels. Values that cross the borders are not shown in these figures. Boxes in the funnel plot indicated the studies included in this meta- analysis.

Figure 6. The sensitivity, specificity, diagnostic OR, SROC curve with AUC and funnel plot for miR-208b levels of 6 studies in the diagnosis of myocardial infarction.

(A) Sensitivity. (B) Specificity. (C) Diagnostic OR. (D) SROC curve with AUC. (E) Funnel plot. Df, degree of freedom; OR, odds ratio; SROC, summary receiver operator characteristics; AUC, area under the curve; SE, standard error; Q*, Q index. Balls, estimated respectively the sensitivity, specificity, diagnostic OR, AUC; Bars, 95% confidence intervals (CIs); Width of diamonds, pooled CIs. The size of each ball is proportional to the weight of each study in the meta-analysis. The SROC show all values of AUC and the area between the upper left and lower right curves represent the CIs of AUC for total miRNA levels. Values that cross the borders are not shown in these figures. Boxes in the funnel plot indicated the studies included in this meta- analysis.