Plasma microRNA Profiles as a Potential Biomarker in Differentiating Adult-Onset Still's Disease From Sepsis
Plasma microRNA Profiles as a Potential Biomarker in Differentiating Adult-Onset Still's Disease From Sepsis
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血浆 microRNA 谱可作为区分成人斯蒂尔病和脓毒症的潜在生物标志物
DOI：
10.3389/fimmu.2018.03099
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发表时间：
2019-01-11
影响因子：
7.3
通讯作者：
Shi, Hui
中科院分区：
文献类型：
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作者：
Hu, Qiongyi;Gong, Wen;Shi, Hui
成人斯蒂尔病（AOSD）是一种以细胞因子风暴为特征的全身性炎症性疾病。然而，临床上用于AOSD的诊断检测方法尚未得到验证。我们研究的目的是寻找具有高特异性和敏感性的非侵入性生物标志物，以用于AOSD的诊断。通过微小RNA（miRNA）深度测序分析了未经任何治疗的初发AOSD患者外周血单个核细胞（PBMC）和健康对照者（HCs）的miRNA表达谱。使用100例AOSD患者和60例健康对照者的血浆样本，通过定量逆转录聚合酶链反应（qRT-PCR）验证miRNA的表达水平。运用先进的统计模型分析miRNA表达水平与临床表现之间的相关性。我们发现，AOSD患者的血浆样本呈现出独特的miRNA表达谱。在训练集和验证集中，与健康对照者相比，AOSD患者血浆中的5种miRNA（miR - 142 - 5p、miR - 101 - 3p、miR - 29a - 3p、miR - 29c - 3p和miR - 141 - 3p）显著上调。我们发现一个包含3种miRNA（miR - 142 - 5p、miR - 101 - 3p和miR - 29a - 3p）的组合，在训练集和验证集中，其受试者工作特征（ROC）曲线下面积为0.8250，可预测AOSD的患病概率。此外，与病情不活动的患者相比，病情活动的AOSD患者中这5种miRNA的表达水平显著更高。另外，在有发热、咽痛和关节痛症状的AOSD患者中发现miR - 101 - 3p水平升高；miR - 101 - 3p还与血清中白细胞介素 - 6（IL - 6）和肿瘤坏死因子 - α（TNF - α）水平呈正相关。再者，AOSD患者血浆中表达的5种miRNA（miR - 142 - 5p、miR - 101 - 3p、miR - 29c - 3p、miR - 29a - 3p和miR - 141 - 3p）显著高于脓毒症患者（P < 0.05）。用于区分AOSD患者和脓毒症患者的4种miRNA组合（miR - 142 - 5p、miR - 101 - 3p、miR - 29c - 3p和miR - 141 - 3p）的ROC曲线下面积（AUC）值为0.8448，揭示了其在区分AOSD患者和脓毒症患者方面潜在的诊断价值。我们的研究结果确定了一种特定的血浆miRNA特征，其有可能作为一种潜在的非侵入性生物标志物，用于AOSD的诊断和疾病活动监测。
Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by cytokine storm. However, a diagnostic test for AOSD in clinical use is yet to be validated. The aim of our study was to identify non-invasive biomarkers with high specificity and sensitivity to diagnosis of AOSD. MicroRNA (miRNA) profiles in PBMC from new-onset AOSD patients without any treatment and healthy controls (HCs) were analyzed by miRNA deep sequencing. Plasma samples from 100 AOSD patients and 60 HCs were used to validated the expression levels of miRNA by qRT-PCR. The correlations between expression levels of miRNAs and clinical manifestations were analyzed using advanced statistical models. We found that plasma samples from AOSD patients showed a distinct miRNA expression profile. Five miRNAs (miR-142-5p, miR-101-3p, miR-29a-3p, miR-29c-3p, and miR-141-3p) were significantly upregulated in plasma of AOSD patients compared with HCs both in training and validation sets. We discovered a panel including 3 miRNAs (miR-142-5p, miR-101-3p, and miR-29a-3p) that can predict the probability of AOSD with an area under the receiver operating characteristic (ROC) curve of 0.8250 in training and validation sets. Moreover, the expression levels of 5 miRNAs were significantly higher in active AOSD patients compared with those in inactive patients. In addition, elevated level of miR-101-3p was found in AOSD patients with fever, sore throat and arthralgia symptoms; the miR-101-3p was also positively correlated with the levels of IL-6 and TNF-α in serum. Furthermore, five miRNAs (miR-142-5p, miR-101-3p, miR-29c-3p, miR-29a-3p, and miR-141-3p) expressed in plasma were significantly higher in AOSD patients than in sepsis patients (P < 0.05). The AUC value of 4-miRNA panel (miR-142-5p, miR-101-3p, miR-29c-3p, and miR-141-3p) for AOSD diagnosis from sepsis was 0.8448, revealing the potentially diagnostic value to distinguish AOSD patients from sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as a potential non-invasive biomarker for diagnosis of AOSD and monitoring disease activity.