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循环 miR-140-3p、miR-130a-3p 和 miR-320b 表达水平作为急性缺血性脑卒中的诊断生物标志物。

The expression levels of circulating miR-140-3p, miR-130a-3p, and miR-320b as diagnostic biomarkers in acute ischemic stroke.

机构信息

Department of Neurology, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China.

Health Management Center, Sichuan Provincial People' s Hospital, Chengdu, Sichuan, China.

出版信息

Kaohsiung J Med Sci. 2023 Sep;39(9):927-935. doi: 10.1002/kjm2.12721. Epub 2023 Jun 20.

Abstract

Plasma miRNAs can characterize several diseases, including acute ischemic stroke (AIS), which is noninvasive and currently affordable in most laboratories worldwide. We aimed to demonstrate plasma miR-140-3p, miR-130a-3p, and miR-320b as diagnostic biomarkers in AIS.GSE110993 and GSE86291 datasets were analyzed to obtain plasma differentially expressed miRNAs between AIS and healthy control subjects (HCs). We further applied RT-qPCR for the validation in 85 AIS patients and 85 HCs. Receiver operating characteristic (ROC) curve were conducted to evaluate their diagnostic utility in AIS. Correlation was analyzed between DEmiRNAs and clinical and laboratory parameters, as well as inflammatory markers. The plasma levels of miR-140-3p, miR-130a-3p, and miR-320b were found to be consistently altered in both GSE110993 and GSE86291 datasets. In comparison to HCs, AIS patients at admission exhibited lower levels of miR-140-3p and miR-320b and higher level of miR-130a-3p in their plasma. The ROC analysis revealed that plasma miR-140-3p, miR-130a-3p, and miR-320b had area under the curve values of 0.790, 0.831, and 0.907, respectively. When combined, these miRNAs showed superior discriminatory power with a sensitivity of 91.76% and specificity of 95.29%. Plasma miR-140-3p and miR-320b negatively correlated glucose levels and inflammatory markers (IL-6, MMP-2, MMP-9, and VEGF) in AIS patients. Conversely, plasma miR-130a-3p levels were positively associated with glucose levels and these markers. Plasma miR-140-3p, miR-130a-3p, and miR-320b levels varied significantly among AIS patients with different NIHSS scores. Plasma miR-140-3p, miR-130a-3p, and miR-320b had high diagnostic value in AIS patients, which were correlated with inflammation and severity in stroke.

摘要

血浆 miRNA 可用于表征多种疾病,包括急性缺血性脑卒中(AIS)。AIS 具有非侵入性,且目前在世界大多数实验室都能负担得起相关检测费用。本研究旨在验证血浆 miR-140-3p、miR-130a-3p 和 miR-320b 是否可作为 AIS 的诊断生物标志物。我们分析了 GSE110993 和 GSE86291 数据集,以获取 AIS 患者与健康对照组(HC)之间血浆差异表达 miRNA。进一步应用 RT-qPCR 对 85 例 AIS 患者和 85 例 HCs 进行验证。通过绘制受试者工作特征(ROC)曲线评估其在 AIS 中的诊断价值。分析差异表达 miRNA 与临床和实验室参数以及炎症标志物之间的相关性。结果显示,GSE110993 和 GSE86291 数据集中均一致发现血浆 miR-140-3p、miR-130a-3p 和 miR-320b 水平发生改变。与 HCs 相比,入院时 AIS 患者的血浆 miR-140-3p 和 miR-320b 水平降低,miR-130a-3p 水平升高。ROC 分析显示,血浆 miR-140-3p、miR-130a-3p 和 miR-320b 的曲线下面积分别为 0.790、0.831 和 0.907。当联合使用这些 miRNA 时,具有较高的鉴别能力,其敏感性为 91.76%,特异性为 95.29%。AIS 患者的血浆 miR-140-3p 和 miR-320b 与血糖水平和炎症标志物(IL-6、MMP-2、MMP-9 和 VEGF)呈负相关,而血浆 miR-130a-3p 水平与血糖水平和这些标志物呈正相关。不同 NIHSS 评分的 AIS 患者的血浆 miR-140-3p、miR-130a-3p 和 miR-320b 水平差异显著。血浆 miR-140-3p、miR-130a-3p 和 miR-320b 在 AIS 患者中具有较高的诊断价值,与卒中后的炎症和严重程度相关。

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