Institute of Genomic Medicine, Wenzhou Medical University.
Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University.
Rheumatology (Oxford). 2020 Sep 1;59(9):2603-2615. doi: 10.1093/rheumatology/keaa163.
This study aims to characterize the expression profiles of circRNAs in primary Sjogren's Syndrome (pSS) and examine the potential of noninvasive circular RNAs (circRNAs) as biomarkers of pSS.
We performed RNA sequencing of minor salivary gland (MSG) biopsies from four pSS and four non-pSS individuals (subjects undergoing MSG biopsies but not meeting 2012 or 2016 ACR classification criteria for SS). Differentially expressed circRNAs were identified by DESeq2, and confirmed by quantitative real-time PCR in the MSGs as well as in plasma exosomes in 37 pSS and 14 non-pSS subjects. Discriminatory capacity testing using receiver operating characteristic analysis was used to evaluate the performance of circRNAs as diagnostic biomarkers for pSS.
Circ-IQGAP2 and circ-ZC3H6 had significantly upregulated expression in the MSGs of pSS patients, and this elevated expression was confirmed by quantitative real-time PCR of plasma exosome RNA. The expression of these circRNAs also showed significant correlation with both clinical features, serum IgG level and MSG focus scores. Receiver operating characteristic analysis showed that the indices comprised of both the two circRNAs and clinical features were better able to distinguish pSS from non-pSS subjects with high mean areas under the curve of 0.93 in the MSGs and 0.92 in the plasma exosomes.
This study indicated the potential roles of circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers for the diagnosis of pSS.
本研究旨在描绘原发性干燥综合征（pSS）中小唾液腺（MSG）中 circRNAs 的表达谱，并探究循环 RNA（circRNAs）作为 pSS 生物标志物的潜在价值。
我们对 4 名 pSS 患者和 4 名非 pSS 个体（行 MSG 活检但不符合 2012 年或 2016 年 ACR pSS 分类标准的个体）的 MSG 活检组织进行了 RNA 测序。通过 DESeq2 鉴定差异表达的 circRNAs，并用定量实时 PCR 在 37 名 pSS 患者和 14 名非 pSS 患者的 MSG 及血浆外泌体中对其进行验证。使用受试者工作特征分析评估 circRNAs 作为 pSS 诊断生物标志物的性能。
在 pSS 患者的 MSG 中，circ-IQGAP2 和 circ-ZC3H6 的表达显著上调，这一结果通过对血浆外泌体 RNA 的定量实时 PCR 得到了验证。这些 circRNAs 的表达与临床特征、血清 IgG 水平和 MSG 焦点评分均具有显著相关性。受试者工作特征分析显示，包含这两个 circRNAs 和临床特征的指标在 MSG 中的曲线下面积均值为 0.93，在血浆外泌体中为 0.92，能更好地区分 pSS 患者与非 pSS 个体。
本研究表明 circ-IQGAP2 和 circ-ZC3H6 可能作为 pSS 诊断的非侵入性生物标志物。
