Multi‐omics analysis reveals the interaction between the complement system and the coagulation cascade in the development of endometriosis

Abstract

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.

Serum Proteomics Combined with Metabolomics Analysis Explore the Molecular Biological Characteristics of Eruptive Syringoma

“…A crosstalk was detected between complement and coagulation cascades in cancer, septicemia, endometriosis and other diseases. 21 Additionally, we found an abnormal expression of the central complement factors (C4B, GC, C3, and C4A) in ES, suggesting that the ES pathogenesis may be associated with the abnormal status of complements. Human complement C4 is a complex and diverse protein.…”

RNA Sequencing Reveals the Differentially Expressed circRNAs between Stable and Unstable Carotid Atherosclerotic Plaques

“…The potential functions of the upregulated circRNAs in unstable plaques were predicated by the annotation of GO terms and analysis of KEGG pathways using clusterProfiler in R package. There were three GO categories for enriched host genes, namely, biological process (BP), cell component (CC), and molecular function (MF) [ 14 ]. P value <0.05 represented the significance of enriched terms or KEGG pathways.…”

Pitfalls in complement analysis: A systematic literature review of assessing complement activation

“…An imbalance in complement activation and regulation can lead to life-threatening conditions such as coagulation dysregulation, systemic inflammation and failure of organs such as the eyes, kidneys, skin, brain and vascular system ( 75 – 77 ). Because of the large number of complement-mediated diseases, together with recent results from large-scale genomics and proteomic studies ( 78 , 79 ), the interest in the complement system has renewed, especially as a promising target for therapeutic intervention. This was demonstrated more than a decade ago by the first complement-specific drug, eculizumab (Soliris, Alexion), targeting the key complement component C5 ( 29 ).…”