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Translational Stroke Research

, Volume 10, Issue 4, pp 352–361 | Cite as

Using Extracellular Circulating microRNAs to Classify the Etiological Subtypes of Ischemic Stroke

  • YaXing GuiEmail author
  • ZhongPing Xu
  • Tao Jin
  • LiSan Zhang
  • LiLi Chen
  • Bin Hong
  • Fei Xie
  • Wen Lv
  • XingYue Hu
Original Article

Abstract

There is no effective biological method to classify ischemic stroke subtypes. In this study, we first performed a systematical gene array study on serum microRNAs with different ischemic stroke subtypes including 13 normal control subjects (NCs) and 87 ischemic stroke (IS) patients including 23 cardioembolism (CARD), 26 large artery atherosclerosis (LAA), 27 lacunar infarct (LAC), and 11 stroke of undetermined etiology (SUE). Validation was performed by using an independent cohort of 20 NCs and 85 IS patients including 28 CARD, 23 LAA, 18 LAC, and 16 SUE. In the pilot discovery gene array study, we found specific serum microRNA signatures between different ischemic stroke subtypes (CARD, LAA, LAC, and SUE). We further validated 6 microRNAs [miR-125b, miR-125a, let-7b, let-7e, miR-7-2-3p, miR-1908] in a different group of ischemic stroke subtypes by using an independent cohort of 20 NCs, 28 CARD, 23 LAA, 18 LAC, and 16 SUE. Moreover, these circulating miRNAs were further detected to be differentially expressed between pre- vs. post-stroke in different ischemic stroke subtypes. The ROC analysis showed that miR-125b, miR-125a, let-7b, and let-7e could discriminate CARD patients from normal controls and other subtypes. Furthermore, ROC curves shown that miR-7-2-3p and miR-1908 showed significant area-under-the-curve values in both LAA and LAC patients. In conclusion, these results demonstrated that circulating miRNAs in sera could be potentially novel risk factors that involve in the pathogenesis of ischemic stroke subtypes.

Keywords

Ischemic stroke Subtype MicroRNA 

Notes

Author Contribution

YXG, ZPX, TJ, LSZ, LLC, and BH performed the experiments and data analysis. FX, WL, and XYH collected the subject’s samples and clinical data. All the authors contributed to the manuscript writing and revision.

Funding Information

This study was funded by National Natural Science Foundation of China (81401038) and the Project of Chinese Medicine Science and Technology of Department of Zhejiang Province (2018ZB076). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Written informed consent for participation in the study was obtained from either directly or from his or her guardian in all subjects and the work received approval from the institution ethics committee of Zhejiang University School of Medicine and in accordance with the tenets of the Declaration of Helsinki.

Supplementary material

12975_2018_659_Fig3_ESM.png (31 kb)
Supplemental Figure 1

Principal component analysis. The plots for ischemic stroke subtypes (13 NC, 23 CARD, 26 LAA, 27 LAC, and 11 SUE) were performed as principal component analysis among all samples based on miRNA profiles. (PNG 31.4 kb)

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High Resolution Image (TIF 3095 kb)
12975_2018_659_Fig4_ESM.png (187 kb)
Supplemental Figure 2

ROC curves for miRNAs that are significantly different in CARD patients as compared to normal controls. ROC curve was performed with AUC for miR-125b, miR-125a, let-7b, and let-7e. (PNG 186 kb)

12975_2018_659_MOESM2_ESM.tif (9.2 mb)
High Resolution Image (9426 kb)
12975_2018_659_Fig5_ESM.png (91 kb)
Supplemental Figure 3

ROC curves for miRNAs that are significantly different in LAA and LAC patients as compared to stable patients. ROC curve was performed with area under the curve (AUC) for miR-7-2-3p, miR-1908. (PNG 91.3 kb)

12975_2018_659_MOESM3_ESM.tif (4.3 mb)
High Resolution Image (4442 kb)
12975_2018_659_MOESM4_ESM.docx (21 kb)
Supplemental Table 1 (20.6 kb)
12975_2018_659_MOESM5_ESM.docx (21 kb)
Supplemental Table 2 (21.3 kb)
12975_2018_659_MOESM6_ESM.docx (21 kb)
Supplemental Table 3 (20.5 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • YaXing Gui
    • 1
    Email author
  • ZhongPing Xu
    • 2
  • Tao Jin
    • 1
  • LiSan Zhang
    • 1
  • LiLi Chen
    • 1
  • Bin Hong
    • 1
  • Fei Xie
    • 1
  • Wen Lv
    • 1
  • XingYue Hu
    • 1
  1. 1.Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Washington University School of MedicineSt. LouisUSA

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