The value of serum microRNA combined detection for early diagnosis of acute aortic dissection

Objective: To investigate the value of serum microRNA (miRNA) levels in the early diagnosis of acute aortic dissection (AAD).

Methods: (1) Human umbilical vein endothelial cells (HUVEC) were transfected with hsa-miR-744-5p mimic and its negative control mimic, and cell proliferation and migration were assessed using the CCK-8 assay and wound healing assay. (2) A total of 40 patients diagnosed with AAD by whole-aorta CT angiography in the Emergency Department of the First Affiliated Hospital of Xinjiang Medical University from January 2020 to January 2022 were enrolled as the AAD group. The time interval between chest pain onset and blood sample collection was less than 24 hours. Meanwhile, 40 age- and sex-matched healthy individuals undergoing routine physical examinations were selected as the control group. The initial blood samples were collected from AAD patients upon admission, while fasting blood samples were collected from the control group. Based on our previous research findings, the top 10 miRNAs with the highest fold-change (>1) and the most significant upregulation were identified. Through a literature review, three miRNAs (miR-206, miR-143-3p, and miR-744-5p) were selected as target miRNAs. Laboratory test results, including D-dimer levels, were collected from both groups. The relative expression levels of target miRNAs in both groups were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman correlation analysis was performed to assess the correlation of target miRNA expression levels. Receiver operating characteristic (ROC) curves were plotted to calculate the area under the curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy.

Results: (1) The CCK-8 assay showed that compared with HUVEC transfected with negative control mimic, HUVEC transfected with hsa-miR-744-5p exhibited lower absorbance values at all time points (all P<0.05). The wound healing assay indicated that the relative migration rate of HUVEC transfected with hsa-miR-744-5p mimic was significantly lower (P<0.05). (2) The D-dimer level significantly differed between the AAD group and the control group (1 737.0 (660.5, 3 297.5) μg/L vs. 66.0 (34.0, 89.0) μg/L, P<0.001). The expression levels of all three miRNA in the serum of AAD patients were significantly upregulated compared with the control group by qRT-PCR (all P<0.05). Spearman correlation analysis revealed positive correlations between miR-206 and miR-744-5p (r=0.508, P<0.001), miR-143-3p and miR-744-5p (r=0.695, P<0.001), and miR-206 and miR-143-3p (r=0.651, P<0.001). All three miRNAs had diagnostic value for AAD in ROC analysis, with miR-206 demonstrating the highest diagnostic accuracy (67.50%) and a specificity of 92.5%. The combined detection of miRNA improved diagnostic accuracy, with miR-206+miR-143-3p achieving an accuracy of 71.25%, specificity of 100%, and positive predictive value of 100%. The combination of miRNA with D-dimer further enhanced diagnostic accuracy, with miR-206+miR-744-5p+D-dimer achieving the highest accuracy (97.50%), along with sensitivity, specificity, positive predictive value, and negative predictive value all at 97.5%. The diagnostic performance of miR-206+miR-143-3p+miR-744-5p+D-dimer was identical to that of miR-206+miR-744-5p+D-dimer.

Conclusion: miR-206, miR-143-3p, and miR-744-5p show great potential for the early diagnosis of acute aortic dissection, and their combination with D-dimer can significantly improve diagnostic sensitivity, specificity and accuracy.