Zheng Lei, Zhuang Chunbo, Wang Xiaobei, Ming Liang
Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Clin Lab Anal. 2018 Feb;32(2). doi: 10.1002/jcla.22266. Epub 2017 May 31.
Previous studies have demonstrated that dysfunctional regulatory T cells (Tregs) may be associated with Graves' disease (GD). In this study, we evaluated four serum Treg-associated miRNAs (miR-210, miR-182, miR-155, and miR-146a) expressions and assessed the potential of serum miRNAs as biomarkers of GD.
Foxp3 and serum miRNAs expressions both in GD patients and healthy controls were measured by RT-PCR.
Serum miR-210 in GD patients was significantly higher than that of healthy controls (2.64-fold, P<.001); in contrast, miR-155 and miR-146a were lower (P<.001 and P=.008). No significant difference was found in miR-182. ROC curve analysis indicated that miR-210, miR-155, and miR-146a with the area under ROC (AUC) of 0.803 (70.0% sensitivity and 83.1% specificity), 0.796 (76.3% sensitivity and 76.9% specificity), and 0.736 (68.8% sensitivity and 73.8% specificity), respectively, could differentiate GD patients from healthy controls. Combination of three miRNAs yielded an AUC of 0.976 (91.3% sensitivity and 93.8% specificity) with 92.41% diagnostic efficiency. In addition, serum miR-210 and miR-155 in GD were associated with the extent of goiter. Three miRNAs levels were different by gender. Besides, serum miR-210 was positively correlated with free thyroxine (FT4) and thyrotrophin receptor antibody (TRAb) level.
The serum levels of miR-210, miR-155, and miR-146a may be potential new markers for the diagnosis of GD and play important roles in GD pathogenesis.
既往研究表明，功能失调的调节性T细胞（Tregs）可能与格雷夫斯病（GD）相关。在本研究中，我们评估了四种血清Treg相关的微小RNA（miR-210、miR-182、miR-155和miR-146a）的表达，并评估了血清微小RNA作为GD生物标志物的潜力。
采用逆转录聚合酶链反应（RT-PCR）检测GD患者和健康对照者中Foxp3和血清微小RNA的表达。
GD患者血清miR-210显著高于健康对照者（2.64倍，P<0.001）；相反，miR-155和miR-146a较低（P<0.001和P=0.008）。miR-182未发现显著差异。ROC曲线分析表明，miR-210、miR-155和miR-146a的ROC曲线下面积（AUC）分别为0.803（灵敏度70.0%，特异性83.1%）、0.796（灵敏度76.3%，特异性76.9%）和0.736（灵敏度68.8%，特异性73.8%），可区分GD患者和健康对照者。三种微小RNA联合检测的AUC为0.976（灵敏度91.3%，特异性93.8%），诊断效率为92.41%。此外，GD患者血清miR-210和miR-155与甲状腺肿大程度相关。三种微小RNA水平在性别上存在差异。此外，血清miR-210与游离甲状腺素（FT4）和促甲状腺素受体抗体（TRAb）水平呈正相关。
血清miR-210、miR-155和miR-146a水平可能是GD诊断的潜在新标志物，并在GD发病机制中起重要作用。
