Abstract

Background: MircroRNA (MiRNA) levels are associated with disease pathophysiology and are high in plasma exosomes. Plasma exosomal miRNAs serve as potential therapeutic targets and diagnosis biomarkers in some diseases but few studies have examined them in Ischemic Stroke (IS). Therefore, we explored the potential predictive value of plasma exosomal miR-422a and miR-125b-2-3p in different IS phases (acute and subacute phases).

Methods: Fifty-five IS patients and 25 age and sex matched healthy controls were recruited. Patients were classified into two groups: 27 patients in acute phase (days 1-3) and 28 patients in subacute phase (days 4-14). The plasma exosomal levels of miR-422a and miR-125b-2-3p were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The Areas Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve were constructed to evaluate the diagnostic accuracy of these miRNAs in IS.

Results: The expression levels of plasma exosomal miR-422a and miR-125b-2-3p were significantly decreased in the subacute phase group (P<0.001, P<0.001, respectively), and the miR-422a levels were increased in the acute phase group (P<0.005) as compared to the controls. Additionally, the expression levels of plasma exosomal miR-422a and miR-125b-2-3p were significantly decreased in the subacute phase group than in the acute phase group (P<0.001, P<0.005, respectively). ROC analysis showed high AUC values for miR-422a and miR-125b-2-3p in the subacute phase group as compared to those in healthy controls: 0.971 and 0.889, respectively, and miR-422a in the acute phase group as compared to healthy controls were 0.769.

Conclusion: Plasma exosomal miR-422a and miR-125b-2-3p may serve as blood-based biomarkers for monitoring and diagnosing in IS patients, with plasma exosomal miR-422a showing the best diagnostic value. The use of these two plasma exosomal miRNAs in combination may be powerful for determining IS stage.

Keywords: Ischemic stroke, plasma exosomes, biomarker, miR-422a, miR-146a, miR-125b-2-3p.