Luo Jing, Liao Xin, Zhang Lihe, Xu Xin, Ying Senhong, Yu Mengjiao, Zhu Lixia, Lin Suxian, Wang Xiaobing
Rheumatology Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, China.
Front Cell Dev Biol. 2020 Dec 4;8:592490. doi: 10.3389/fcell.2020.592490. eCollection 2020.
Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by exocrine gland damage and extraglandular involvements. To identify potential biomarkers for the early detection of pSS and to further investigate the potential roles of the biomarkers in the progression of pSS, our previous RNA sequencing data and four microarray data of salivary glands (SGs) were combined for integrative transcriptome analysis between pSS and non-pSS. Differential gene expression analysis, gene co-expression network analysis, and pathway analysis were conducted to detect hub genes, which were subsequently investigated in peripheral blood mononuclear cell (PBMC) and plasma. Correlation analysis, single-gene Gene Set Enrichment Analysis, and receiver operating characteristic (ROC) curve were applied to investigate the potential function of the hub genes and their classification capacity for pSS. A total of 51 common up-regulated genes were identified among different pSS cohorts. A key module was found to be the most closely linked to pSS, which was significantly associated with inflammation-related pathways. Seven overlapped hub genes (, , , , , , and ) were identified, among which was demonstrated to be involved in most crucial immune pathways. was up-regulated not only in SGs but also in PBMC and plasma in pSS, and the expression of was closely associated with lymphocytic infiltration in SGs and disease activity of pSS patients. It showed a strong classification capacity with classic clinical index in SGs (ROC curve 0.9821) and significant distinct discrimination in PBMC (ROC curve 0.9107). These findings are expected to gain a further insight into the pathogenesis of pSS and provide a promising candidate for the early detection of pSS.
原发性干燥综合征（pSS）是一种慢性全身性自身免疫性疾病，其特征为外分泌腺损伤和腺体外受累。为了识别用于pSS早期检测的潜在生物标志物，并进一步研究这些生物标志物在pSS进展中的潜在作用，我们将先前的RNA测序数据和四个唾液腺（SGs）的微阵列数据相结合，进行pSS与非pSS之间的综合转录组分析。进行差异基因表达分析、基因共表达网络分析和通路分析以检测枢纽基因，随后在外周血单个核细胞（PBMC）和血浆中对其进行研究。应用相关性分析、单基因基因集富集分析和受试者工作特征（ROC）曲线来研究枢纽基因的潜在功能及其对pSS的分类能力。在不同的pSS队列中总共鉴定出51个共同上调的基因。发现一个关键模块与pSS联系最为紧密，它与炎症相关通路显著相关。鉴定出七个重叠的枢纽基因（、、、、、和），其中被证明参与了最关键的免疫通路。在pSS中不仅在SGs中上调，在PBMC和血浆中也上调，并且的表达与SGs中的淋巴细胞浸润和pSS患者的疾病活动密切相关。它在SGs中与经典临床指标具有很强的分类能力（ROC曲线0.9821），在PBMC中具有显著的明显区分度（ROC曲线0.9107）。这些发现有望进一步深入了解pSS的发病机制，并为pSS的早期检测提供一个有前景的候选标志物。
