Role and predictive value of microRNAs 204 and 210 in the diagnosis of pulmonary arterial hypertension and the distinction between idiopathic, systemic sclerosis, and schistosomiasis-associated pulmonary arterial hypertension

Mark O. Dimitry, Yosef M. Amin, Reem I. ElKorashy, Hala M. Raslan, Solaf A. Kamel, Eman M. Hassan, Rasha N. Yousef, Eman A. Awadallah
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Abstract

Pulmonary arterial hypertension is most of the time diagnosed late in the course of the disease and necessitates right cardiac catheterization which is an invasive and costly tool. MicroRNAs have a role in the pathogenesis of pulmonary hypertension, systemic sclerosis, and schistosomiasis and their dosages are easy and non-expensive. Therefore, determining their levels in the blood may be helpful in detecting PAH and differentiating its idiopathic form from those caused by systemic sclerosis and schistosomiasis. To evaluate the role of microRNA (miR) 204 and miR-210 in the diagnosis of PAH and to distinguish between idiopathic PAH (IPAH), systemic sclerosis-associated PAH (SSc-PAH), and schistosomiasis-associated PAH (Sch-PAH) and to identify patients who may benefit from simple non-expensive and non-invasive methods in diagnosis of PAH. Sixty patients with PAH and 30 subjects as control were enrolled in the study. PAH was diagnosed by right heart catheterization, echocardiography, and laboratory tests. Blood samples were taken from all patients for measuring miR-204 and miR-210. MiR-204 was downregulated in PAH and there was a highly significant difference between PAH and control (p = 0.003) with cut-off predictive value ≤ 0.15 µM and 70% sensitivity, 85% specificity with AUC (0.749). However, miR-204 failed to distinguish between IPAH, SSc-PAH, and Sch-PAH. MiR-210 was upregulated in PAH with a highly significant difference between PAH and control (p < 0.001) with cut-off predictive value ≥ 1.16 µM and 93.33% sensitivity, 85% specificity with AUC (0.917). MiiR-210 showed a significant difference between SSc-PAH and idiopathic PAH (P = 0.012) and between SSc-PAH and Sch-PAH (P = 0.035). MiR-204 and miR-210 are useful non-invasive and non-expensive markers for the diagnosis of PAH, miR-210 is an excellent predictor in the diagnosis of PAH and also miR-210 might be used to distinguish SSc-PAH from idiopathic PAH and Sch-PAH.
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微小RNA 204和210在肺动脉高压诊断中的作用和预测价值,以及特发性、系统性硬化症和血吸虫病相关肺动脉高压的区别
肺动脉高压大多在病程晚期才被诊断出来,必须进行右心导管检查,这是一种侵入性和昂贵的工具。微小核糖核酸在肺动脉高压、系统性硬化症和血吸虫病的发病机制中发挥着作用,而且其用量简单、成本低廉。因此,测定其在血液中的水平可能有助于检测 PAH,并将特发性 PAH 与系统性硬化症和血吸虫病引起的 PAH 区分开来。目的:评估微RNA(miR)204和miR-210在诊断PAH中的作用,并区分特发性PAH(IPAH)、系统性硬化相关性PAH(SSc-PAH)和血吸虫病相关性PAH(Sch-PAH),确定哪些患者可能受益于诊断PAH的简单、非昂贵和非侵入性方法。研究共招募了 60 名 PAH 患者和 30 名对照组受试者。PAH 是通过右心导管检查、超声心动图和实验室检测诊断出来的。研究人员采集了所有患者的血液样本,用于测量 miR-204 和 miR-210。MiR-204在PAH患者中下调,PAH患者与对照组之间存在非常显著的差异(p = 0.003),临界预测值≤ 0.15 µM,灵敏度为70%,特异度为85%,AUC为0.749。然而,miR-204 无法区分 IPAH、SSc-PAH 和 Sch-PAH。MiR-210在PAH中上调,PAH和对照组之间的差异非常显著(p < 0.001),临界预测值≥ 1.16 µM,灵敏度为93.33%,特异度为85%,AUC(0.917)。MiiR-210在SSc-PAH和特发性PAH之间(P = 0.012)以及SSc-PAH和Sch-PAH之间(P = 0.035)显示出显著差异。miR-204和miR-210是诊断PAH的非侵入性和非昂贵的有用标记物,miR-210是诊断PAH的极佳预测因子,miR-210还可用于区分SSc-PAH与特发性PAH和Sch-PAH。
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