Circulating MicroRNA-4739 May Be a Potential Biomarker of Critical Limb Ischemia in Patients with Diabetes

Circulating MicroRNA-4739 May Be a Potential Biomarker of Critical Limb Ischemia in Patients with Diabetes
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循环 MicroRNA-4739 可能是糖尿病患者严重肢体缺血的潜在生物标志物。

DOI:
10.1155/2018/4232794
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发表时间:
2018-01-01
影响因子:
--
通讯作者:
Deng, Ai-ping
Deng, Ai-ping
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Ju-yi;Cheng, Biao;Deng, Ai-ping

文献摘要

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临界肢体缺血(CLI)是周围动脉疾病的最严重表现,这很常见,但很少被诊断出。迫切需要非侵入性生物标志物来帮助诊断CLI。积累的证据表明,miRNA在各种疾病的发展中起着重要作用。在这项研究中,微阵列分析显示11个miRNA在四名T2DM CLI患者中的表达明显改变,而在没有CLI的四个性别和年龄匹配的T2DM患者中,其表达。在独立队列中,QRT-PCR验证证实了CLI与没有CLI患者的患者中miRNA-4739水平升高。 MiRNA-4739水平随FPG和HBA1C的水平升高(全p <0.05)。调整了风险因素后,发现miRNA-4739水平与CLI的比值比(OR)增加(OR = 12.818,95%置信区间(CI)1.148至143.143,p = 0.038)。 ROC曲线分析表明,miR-4739+混淆风险因素的曲线(AUC)面积为0.94(95%CI 0.891至0.998,p <0.001),高于混淆风险因素(AUC 0.94 vs. 0.94 vs. 0.91,95%CI -0.0.122至0.093)和0.03.093和0.033和0.055(air air a)。分别为0.69,95%CI -0.399至-0.101,p <0.001)。我们得出的结论是,T2DM患者的血浆miRNA-4739水平与CLI独立相关。 miRNA-4739与糖尿病中CLI的潜在治疗靶标有关。
Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease, which is common but rarely diagnosed. Noninvasive biomarkers are urgently required to assist in the diagnosis of CLI. Accumulating evidence indicates that miRNAs play an important role in the development of various diseases. In this study, microarray profiling revealed 11 miRNAs with significantly altered expression in four T2DM patients with CLI compared with that in four sex-and age-matched T2DM patients without CLI. In independent cohorts, qRT-PCR validation confirmed the increased miRNA-4739 level in patients with CLI versus patients without CLI. miRNA-4739 levels increased with FPG and HbA1c (all P < 0.05). After adjusting for the risk factors, miRNA-4739 levels were found to be associated with an increased odds ratio (OR) of T2DM with CLI (OR = 12.818, 95% confidence intervals (CI) 1.148 to 143.143, P = 0.038). ROC curve analysis revealed that the area under the curve (AUC) of miR-4739+confounding risk factors was 0.94 (95% CI 0.891 to 0.998, P < 0.001), which was higher than that of confounding risk factors (AUC 0.94 vs. 0.91, 95% CI -0.122 to 0.060, P > 0.05) and of miR-4739 (AUC 0.94 vs. 0.69, 95% CI -0.399 to -0.101, P < 0.001), respectively. We conclude that elevated plasma miRNA-4739 levels are independently associated with CLI in T2DM patients. miRNA-4739 is implicated as a novel diagnostic marker and a potential therapeutic target for CLI in diabetes.