Circulating Non-coding RNAs as Potential Biomarkers for Ischemic Stroke: A Systematic Review

Abstract

Background: Recent studies have demonstrated that dysregulated non-coding RNAs (ncRNAs) are involved in the pathogenesis of ischemic stroke (IS), including neuroinflammation, apoptosis, atherosclerosis, and angiogenesis. However, discrepant results make it difficult to apply ncRNAs to clinical practice. Therefore, we performed a meta-analysis to evaluate and elucidate the diagnostic value of ncRNAs in IS.

Methods: We searched the literature in four databases-PubMed, Web of Science, EMBASE, and the Cochrane Library-up to December 31, 2020, to identify the relationship between differentially expressed ncRNAs and IS. Pooled sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the diagnostic performance of ncRNAs.

Results: Fifteen studies on microRNAs (miRNAs) including 1687 IS patients and eight studies on long non-coding RNAs (lncRNAs) including 741 IS patients were included in our study. Estimates of the identification efficiency of miRNAs from the 15 studies were as follows: 0.76 (95% CI: 0.67-0.84) for sensitivity (SEN), 0.83 (95% CI: 0.77-0.88) for specificity (SPE), 4.5 (95% CI: 3.4-6.1) for PLR, 0.29 (95% CI: 0.20-0.40) for NLR, and 16 (95% CI: 10-26) for DOR. The area under the curve (AUC) of the summary receiver operator characteristic (SROC) curve showed diagnostic accuracy of 0.87 (95% CI: 0.84-0.90); thus the diagnostic value of all the miRNAs was moderate. In addition, the results for lncRNAs were as follows: 0.73 (95% CI: 0.69-0.77) for SEN, 0.75 (95% CI: 0.70-0.79) for SPE, 2.9 (95% CI: 2.4-3.4) for PLR, 0.36 (95% CI: 0.31-0.42) for NLR, 8 (95% CI: 6-11) for DOR, 0.80 (95% CI: 0.76-0.83) for AUC, and a moderate diagnostic value.

Conclusion: Our study revealed that blood-circulating ncRNAs could be a moderately effective candidate biomarker for the diagnosis of IS. Furthermore, the combined lncRNAs showed more accurate diagnostic properties than single lncRNAs, and some single miRNAs (e.g., miR-107) showed better diagnostic performance, which may contribute to IS clinical practice.

Keywords: Biomarker; Diagnosis; Ischemic stroke; lncRNAs; miRNAs.