The State Key Lab of Reproductive, Department of Obstetrics and Gynecology, Jiangsu Province Hospital, Nanjing, 210029, China.
Department of Obstetrics and Gynecology, the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, 213000, China.
Sci Rep. 2021 Jun 7;11(1):11926. doi: 10.1038/s41598-021-90112-x.
Endometriosis (EMS) is a disease that shows immune dysfunction and chronic inflammation characteristics, suggesting a role of complement system in its pathophysiology. To find out the hub genes and pathways involved in the pathogenesis of EMs, three raw microarray datasets were recruited from the Gene Expression Omnibus database (GEO). Then, a series of bioinformatics technologies including gene ontology (GO), Hallmark pathway enrichment, protein-protein interaction (PPI) network and gene co-expression correlation analysis were performed to identify hub genes. The hub genes were further verified by the Real-time quantitative polymerase chain reaction (RT-PCR) and Western Blot (WB). We identified 129 differentially expressed genes (DEGs) in EMs, of which 78 were up-regulated and 51 were down-regulated. Through GO functional enrichment analysis, we found that the DEGs are mainly enriched in cell adhesion, extracellular matrix remodeling, chemokine regulation, angiogenesis regulation, epithelial cell proliferation, et al. In Hallmark pathway enrichment analysis, coagulation pathway showed great significance and the terms in which included the central complement factors. Moreover, the genes were dominating in PPI network. Combined co-expression analysis with experimental verification, we found that the up-regulated expression of complement (C1S, C1QA, C1R, and C3) was positively related to tissue factor (TF) in EMs. In this study, we discovered the over expression complement and the positive correlation between complement and TF in EMs, which suggested that interaction of complement and coagulation system may play a role within the pathophysiology of EMS.
子宫内膜异位症（EMS）是一种表现出免疫功能障碍和慢性炎症特征的疾病，提示补体系统在其病理生理学中起作用。为了找出涉及 EMS 发病机制的关键基因和途径，从基因表达综合数据库（GEO）中招募了三个原始微阵列数据集。然后，通过基因本体论（GO）、标志性途径富集、蛋白质-蛋白质相互作用（PPI）网络和基因共表达相关性分析等一系列生物信息学技术来识别关键基因。通过实时定量聚合酶链反应（RT-PCR）和 Western Blot（WB）进一步验证关键基因。我们鉴定了 129 个在 EMS 中差异表达的基因（DEGs），其中 78 个上调，51 个下调。通过 GO 功能富集分析，我们发现 DEGs 主要富集在细胞黏附、细胞外基质重塑、趋化因子调节、血管生成调节、上皮细胞增殖等方面。在标志性途径富集分析中，凝血途径显示出重要意义，其中包括中心补体因子。此外，基因在 PPI 网络中占主导地位。结合共表达分析和实验验证，我们发现 EMS 中补体（C1S、C1QA、C1R 和 C3）的上调表达与组织因子（TF）呈正相关。在这项研究中，我们发现了 EMS 中补体的过度表达以及补体与 TF 之间的正相关，这表明补体与凝血系统的相互作用可能在 EMS 的病理生理学中发挥作用。
