Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Ophthalmology, Seoul Metropolitan Government-Seoul National University, Boramae Medical Center, Seoul, Korea.
Sci Rep. 2023 Jan 5;13(1):234. doi: 10.1038/s41598-023-27483-w.
The aim of this study is to characterize the microRNA (miRNA) expression signatures in patients with thyroid eye disease (TED) and identify miRNA biomarkers of disease activity. Total RNA was isolated from the sera of patients with TED (n = 10) and healthy controls (HCs, n = 5) using the miRNeasy Serum/Plasma Kit. The NanoString assay was used for the comprehensive analysis of 798 miRNA expression profiles. Analysis of specific miRNA signatures, mRNA target pathway analysis, and network analysis were performed. Patients with TED were divided into two groups according to disease activity: active and inactive TED groups. Differentially expressed circulating miRNAs were identified and tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) tests in the validation cohort. Among the 798 miRNAs analyzed, 173 differentially downregulated miRNAs were identified in TED patients compared to those in the HCs. Ten circulating miRNAs were differentially expressed between the active and inactive TED groups and regarded as candidate biomarkers for TED activity (one upregulated miRNA: miR-29c-3p; nine downregulated miRNAs: miR-4286, miR-941, miR-571, miR-129-2-3p, miR-484, miR-192-5p, miR-502-3p, miR-597-5p, and miR-296-3p). In the validation cohort, miR-484 and miR-192-5p showed significantly lower expression in the active TED group than in the inactive TED group. In conclusion, the expression levels of miR-484 and miR-192-5p differed significantly between the active and inactive TED groups, suggesting that these miRNAs could serve as circulating biomarkers of TED activity, however, these findings need to be validated in further studies.
本研究旨在描绘甲状腺眼病(TED)患者的 microRNA(miRNA)表达特征,并确定疾病活动的 miRNA 生物标志物。使用 miRNeasy Serum/Plasma Kit 从 TED 患者(n=10)和健康对照者(HCs,n=5)的血清中分离总 RNA。使用 NanoString 检测法对 798 种 miRNA 表达谱进行全面分析。进行特定 miRNA 特征分析、mRNA 靶通路分析和网络分析。根据疾病活动将 TED 患者分为两组:活动期 TED 组和非活动期 TED 组。在验证队列中使用定量逆转录聚合酶链反应(qRT-PCR)检测来鉴定和测试差异表达的循环 miRNA。在分析的 798 种 miRNA 中,与 HCs 相比,TED 患者中有 173 种 miRNA 表达下调。在活动期 TED 组和非活动期 TED 组之间有 10 种循环 miRNA 表达差异,被认为是 TED 活动的候选生物标志物(一个上调 miRNA:miR-29c-3p;九个下调 miRNA:miR-4286、miR-941、miR-571、miR-129-2-3p、miR-484、miR-192-5p、miR-502-3p、miR-597-5p 和 miR-296-3p)。在验证队列中,miR-484 和 miR-192-5p 在活动期 TED 组中的表达显著低于非活动期 TED 组。总之,miR-484 和 miR-192-5p 在活动期和非活动期 TED 组之间的表达水平差异显著,表明这些 miRNA 可能作为 TED 活动的循环生物标志物,但这些发现需要进一步研究验证。