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血浆 microRNAs 作为急性静脉血栓栓塞症诊断的潜在生物标志物。

Plasma microRNAs as potential biomarkers in diagnosis of acute venous thromboembolism.

机构信息

Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Department of Interventional Radiology, Tangshan Gongren Hospital, Tangshan, Hebei, China.

出版信息

Clin Hemorheol Microcirc. 2023;84(4):435-448. doi: 10.3233/CH-231820.

DOI:10.3233/CH-231820
PMID:37334587
Abstract

OBJECTIVE

To assess the potential use of plasma microRNAs (miRNAs) in diagnosis of acute venous thromboembolism (VTE).

METHODS

Using BGISEQ-500 sequencing technology, we analyzed the miRNA profile of paired plasma samples from the acute and chronic phases of four patients with unprovoked VTE. Using real-time quantitative polymerase chain reaction (RT-qPCR), we verified nine upregulated named miRNAs in the acute phase in the plasma samples of 54 patients with acute VTE and 39 controls. We then compared the relative expression of the 9 candidate miRNAs between the acute VTE and control group, and plotted the receiver operating characteristic (ROC) curves of the differentially expressed miRNAs. We chose the miRNA with the greatest area under curve (AUC) to evaluate the effect of miRNA on coagulation and platelet function in the plasma samples of 5 healthy volunteers.

RESULTS

The plasma levels of miR-374b-3p, miR-660-5p, miR-378a-3p, miR-425-5p, miR-3613-5p, miR-130b-3p, miR-183-5p, and miR-103b were higher in patients with acute VTE than in the controls, with AUCs of 0.6776, 0.6614, 0.6648, 0.6885, 0.8048, 0.6871, 0.7298, and 0.7498, respectively, and P values of 0.0036, 0.0081, 0.0069, 0.0020,<0.0001, 0.0022, 0.0002, and < 0.0001, respectively. There were no significant differences in miR-193b-5p level between the acute VTE group and the control group. Fibrinogen (Fib), thrombin- antithrombin complex (TAT), tissue plasminogen activator-inhibitor complex (t-PAIC), and TAT/plasmin-α2-plasmin inhibitor complex (PIC) were decreased in the miR-3613-5p group when compared with the control group (P < 0.05) and the mean platelet aggregation rate was increased in the miR-3613 group (P < 0.05).

CONCLUSION

miRNAs can be potential biomarkers for diagnosing acute VTE, and miR-3613-5p may be involved in the formation, coagulation, and platelet functions in acute VTE.

摘要

目的

评估血浆 microRNAs(miRNAs)在急性静脉血栓栓塞症(VTE)诊断中的潜在应用。

方法

使用 BGISEQ-500 测序技术,我们分析了 4 例无诱因 VTE 患者急性期和慢性期配对血浆样本的 miRNA 图谱。使用实时定量聚合酶链反应(RT-qPCR),我们验证了在 54 例急性 VTE 患者和 39 例对照者的血浆样本中急性期上调的 9 种命名 miRNA。然后,我们比较了急性 VTE 组和对照组之间 9 种候选 miRNA 的相对表达,并绘制了差异表达 miRNA 的受试者工作特征(ROC)曲线。我们选择 AUC 最大的 miRNA 来评估 5 名健康志愿者血浆样本中 miRNA 对凝血和血小板功能的影响。

结果

与对照组相比,急性 VTE 患者的血浆 miR-374b-3p、miR-660-5p、miR-378a-3p、miR-425-5p、miR-3613-5p、miR-130b-3p、miR-183-5p 和 miR-103b 水平更高,AUC 分别为 0.6776、0.6614、0.6648、0.6885、0.8048、0.6871、0.7298 和 0.7498,P 值分别为 0.0036、0.0081、0.0069、0.0020、<0.0001、0.0022、0.0002 和<0.0001。急性 VTE 组和对照组 miR-193b-5p 水平无显著差异。与对照组相比,miR-3613-5p 组纤维蛋白原(Fib)、凝血酶-抗凝血酶复合物(TAT)、组织型纤溶酶原激活物-抑制剂复合物(t-PAIC)和 TAT/纤溶酶-α2-纤溶酶抑制剂复合物(PIC)降低(P<0.05),miR-3613 组血小板聚集率升高(P<0.05)。

结论

miRNAs 可能是诊断急性 VTE 的潜在生物标志物,miR-3613-5p 可能参与急性 VTE 的形成、凝血和血小板功能。

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