Abstract
ObjectiveThe aim of the present study is to explore the potential diagnostic and prognostic value of plasma levels of miR‐99 family for patients with acute cerebral infarction (ACI).MethodsA total of 112 patients who have been diagnosed with ACI were enrolled in this study, and 112 healthy volunteers were served as the controls. The plasma of the patients and controls were collected, and total RNAs were isolated, and the expression levels of miR‐99a, miR‐99b, and miR‐100 in the plasma of patients and controls were compared determined by RT‐qPCR methods; moreover, the receiver operating characteristic (ROC) curve has been drawn to determine whether the plasma levels of miR‐99b can distinguish patients with ACI from the controls; furthermore, the short‐term prognosis of the patients was evaluated by glasgow outcome scale (GOS), and the correlation between the plasma levels of miR‐99b and the GOS of the patients was evaluated. Finally, the correlation between the plasma level of miR‐99 and VEGF of ACI patients was analyzed.ResultsIt was observed that miR‐99b was significantly decreased in the plasma of ACI patients compared with the healthy controls (P < .01), while the plasma levels of miR‐99a and miR‐100 showed no significant differences between the patients with ACI and the healthy controls; moreover, the area under the curve (AUC) of miR‐99b for the diagnosis of ACI was 0.8882 (95% confidence interval (CI), 0.8451‐0.9313), suggesting that plasma level of miR‐99b is a sensitive marker to distinguish patients with ACI from the healthy volunteers; furthermore, the serum level of miR‐99b was negatively correlated with GOS score of the patients (r = −.56, P < .001); finally, the plasma level of miR‐99b was negatively correlated with the levels of VEGF (r = −.3013, P = .0012).ConclusionmiR‐99b was down‐regulated in plasma of patients with ACI, and plasma level of miR‐99b may be a potential diagnostic and prognostic marker for the diagnosis and treatment of ACI.
Highlights
We observed that miR-99b was down-regulated in plasma of patients with acute cerebral infarction (ACI) compared with the healthy controls, and miR-99b may serve as a potential diagnostic and prognostic marker for the early diagnosis and prediction of the clinical outcomes of patients with ACI
Zhou et al reported that plasma levels of both miR-21 and miR-24 may function as early diagnostic markers at early stage of ACI18; Wang et al reported that miR-210 may regulate the proliferation and apoptosis of the endothelial cells in ACI19; Zhang et al suggested that miR-29b and miR-424 may serve as prognostic markers and therapeutic targets for the treatment of ACI.[11]
We observed that the expression level of miR-99b was significantly down-regulated in plasma of patients with ACI compared with the controls, and result of receiver operating characteristic curve (ROC) analysis suggested that plasma level of miR-99b is a sensitive biomarker for the diagnosis of ACI (AUC 0.8882, 95% confidence interval (CI), 0.8451-0.9313)
Summary
Stroke is one of the leading causes of death worldwide.[1,2] Strokes can be classified into ischemic and hemorrhagic, and the ischemic stroke can lead to acute cerebral infarction (ACI) in the brain tissue if the local blood flow has not been recovered in a short period of time.[3,4] Results of previous studies indicated that if no rapid clinical decisions were made, ACI can lead to serious sequelae, for example, disability even death.[5,6,7] early diagnosis of ACI is of great importance to improve the therapeutic efficacy and decrease the potential risk of sequelae and mortality. MicroRNAs (miRNAs or miR) belong to the family of the non-coding RNAs. miRNAs were often short in length (about 18-22 nucleotides), and they can negatively regulate the expression of their target genes on post-transcriptional levels.[10,11] The roles of miRNAs in ACI have been reported in many previous studies, and the diagnostic and prognostic value of some circulating miRNAs, for example, miR-124 and miR-29b have been discussed.[11,12]. The roles of miR-99 miRNA family (including miR-99a, miR-99b and miR-100) in cerebrovascular diseases have been reported previously.[13,14,15] Based on the results of a previous animal study, the level of miR-99b in the peripheral blood was down-regulated the brain of rat ACI models,[15] whether miR-99b could serve as a plasma diagnostic and prognostic marker remains unclear. The relative expression of miR-99b was normalized to the level of U6 by 2−ΔΔCt method
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