Qiuming Yao1, Xuan Wang1, Weiwei He2, Zhenyu Song3, Bin Wang1, Jinan Zhang4, Qiu Qin5. 1. Department of Endocrinology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai, 201508, China. 2. Department of Endocrinology, Affiliated Hospital of Yanan University, Shanxi, 716000, China. 3. Department of Urology, Jinshan Hospital of Fudan University, No. 1508 Longhang Road, Jinshan District, Shanghai, 201508, China. 4. Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, China. zhangjinan@hotmail.com. 5. Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, China. yx20160908@163.com.
Abstract
PURPOSE: Recently, it has been confirmed that circulating miRNAs play an important role in disease pathogenesis and can be biomarkers of many autoimmune diseases. However, the knowledge about circulating miRNAs in Graves' disease (GD) is very limited. In this study, we aimed to identify circulating miRNAs as potential biomarkers of GD. METHODS: We recruited 68 participants who met the criteria for GD and healthy controls. The expression profile of miRNAs in plasma was detected using microarrays. We found five interesting miRNAs were differentially expressed between GD and control group and futher validated their relative expression by quantitative real-time PCR. According to their putative target genes predicted by the TargetScan database, we also performed Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses to predict their potential functions and related pathways. RESULTS: Microarray data showed that five miRNAs were differentially expressed in GD and control plasma samples. Among them, miR-16-1-3p, miR-122-5p, miR-221-3p, and miR-762 were upregulated in GD (P < 0.001). In validation stage, we found miR-144-3p was significantly decreased and miR-762 was markedly upregulated in GD plasma (P < 0.01). In addition, miR-762 expression was positively associated with levels of FT3 (r = 0.307, P = 0.038) as well as TRAb (r = 0.302, P = 0.042). The receiver-operating characteristic (ROC) curve analysis showed that both miR-144-3p and miR-762 displayed good sensitivity and specificity in discriminating the GD patients from the rest of subjects with the area under the ROC curve (AUC) of 0.761 (P = 0.001, 95% CI = 0.648-0.875) and 0.737 (P = 0.001, 95% CI = 0.618-0.857), respectively. Combination of miR-144-3p and miR-762 could better discriminate GD patients from healthy controls with AUC of 0.861 (P < 0.001, 95% CI = 0.775-0.947). CONCLUSIONS: We first demonstrated that aberrant levels of plasmic miR-144-3p and miR-762 were associated with GD, which may be biomarkers for GD diagnosis.
PURPOSE: Recently, it has been confirmed that circulating miRNAs play an important role in disease pathogenesis and can be biomarkers of many autoimmune diseases. However, the knowledge about circulating miRNAs in Graves' disease (GD) is very limited. In this study, we aimed to identify circulating miRNAs as potential biomarkers of GD. METHODS: We recruited 68 participants who met the criteria for GD and healthy controls. The expression profile of miRNAs in plasma was detected using microarrays. We found five interesting miRNAs were differentially expressed between GD and control group and futher validated their relative expression by quantitative real-time PCR. According to their putative target genes predicted by the TargetScan database, we also performed Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses to predict their potential functions and related pathways. RESULTS: Microarray data showed that five miRNAs were differentially expressed in GD and control plasma samples. Among them, miR-16-1-3p, miR-122-5p, miR-221-3p, and miR-762 were upregulated in GD (P < 0.001). In validation stage, we found miR-144-3p was significantly decreased and miR-762 was markedly upregulated in GD plasma (P < 0.01). In addition, miR-762 expression was positively associated with levels of FT3 (r = 0.307, P = 0.038) as well as TRAb (r = 0.302, P = 0.042). The receiver-operating characteristic (ROC) curve analysis showed that both miR-144-3p and miR-762 displayed good sensitivity and specificity in discriminating the GDpatients from the rest of subjects with the area under the ROC curve (AUC) of 0.761 (P = 0.001, 95% CI = 0.648-0.875) and 0.737 (P = 0.001, 95% CI = 0.618-0.857), respectively. Combination of miR-144-3p and miR-762 could better discriminate GDpatients from healthy controls with AUC of 0.861 (P < 0.001, 95% CI = 0.775-0.947). CONCLUSIONS: We first demonstrated that aberrant levels of plasmic miR-144-3p and miR-762 were associated with GD, which may be biomarkers for GD diagnosis.
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