Common and specific gene signatures among three different endometriosis subtypes

Abstract

Aims To identify the common and specific molecular mechanisms of three well-defined subtypes of endometriosis (EMs): ovarian endometriosis (OE), peritoneal endometriosis (PE), and deep infiltrating endometriosis (DIE). Methods Four microarray datasets: GSE7305 and GSE7307 for OE, E-MTAB-694 for PE, and GSE25628 for DIE were downloaded from public databases and conducted to compare ectopic lesions (EC) with eutopic endometrium (EU) from EMs patients. Differentially expressed genes (DEGs) identified by limma package were divided into two parts: common DEGs among three subtypes and specific DEGs in each subtype, both of which were subsequently performed with the Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed by common DEGs and five hub genes were screened out from the PPI network. Besides, these five hub genes together with selected interested pathway-related genes were further validated in an independent OE RNA-sequencing dataset GSE105764. Results A total of 54 EC samples from three EMs subtypes (OE, PE, DIE) and 58 EU samples were analyzed, from which we obtained 148 common DEGs among three subtypes, and 729 specific DEGs in OE, 777 specific DEGs in PE and 36 specific DEGs in DIE. The most enriched pathway of 148 shared DEGs was arachidonic acid (AA) metabolism, in which most genes were up-regulated in EC, indicating inflammation was the most common pathogenesis of three subtypes. Besides, five hub genes AURKB, RRM2, DTL, CCNB1, CCNB2 identified from the PPI network constructed by 148 shared DEGs were all associated with cell cycle and mitosis, and down-regulated in EC, suggesting a slow and controlled proliferation in ectopic lesions. The KEGG pathway analysis of specific DEGs in each subtype revealed that abnormal ovarian steroidogenesis was a prominent feature in OE; OE and DIE seems to be at more risk of malignant development since both of their specific DEGs were enriched in the pathways in cancer, though enriched genes were different, while PE tended to be more associated with dysregulated peritoneal immune and inflammatory microenvironment. Conclusion By integrated bioinformatic analysis, we explored common and specific molecular signatures among different subtypes of endometriosis: activated arachidonic acid (AA) metabolism-related inflammatory process and a slow and controlled proliferation in ectopic lesions were common features in OE, PE and DIE; OE and DIE seemed to be at more risk of malignant development while PE tended to be more associated with dysregulated peritoneal immune and inflammatory microenvironment, all of which could deepen our perception of endometriosis.

Establishment of an Immortalized Endometriotic Stromal Cell Line from Human Ovarian Endometrioma

“…Endometriosis is categorized into three subtypes, OE, PE, and DIE. A recent bioinformatic study found that, although there are some common features amongst the different subtypes of endometriosis, PE tended to be more associated with dysregulated peritoneal immune and inflammatory microenvironment while OE and DIE seemed to be at more risk of malignant development [31]. In addition, that report also suggested differences in the lesion microenvironment of three endometriosis subtypes [32].…”

Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models

“…Until now, there have only been a few reports investigating ribonucleotide reductase’s role in endometriosis. One of them is a recent large-scale bioinformatic analysis of previously available microarray datasets, where authors reported RRM2 being downregulated in endometriosis lesions compared to healthy endometrial tissue in the uterus [ 35 ]. Meanwhile they stated that their analysis has limitations by including tissue sample data that were collected from random or unknown menstrual cycle phases.…”

Text Mining and Hub Gene Network Analysis of Endometriosis

“…ESR1 was one of the CDGs and interacted with the hub gene PIK3CA , which was also identified as the hub gene in our study, while other hub genes from our study were not identified as CDGs in Cui's paper. The other excellent paper by Jiang et al integrated four publicly existing microarray datasets including 1 dataset for peritoneal endometriosis (PE), 2 datasets for ovarian endometriosis (OE), and 1 dataset for deep infiltrating endometriosis (DIE) and used the R package limma to identify common and endometriosis subtype-specific DEGs [ 26 ]. Jiang et al found that the PI3K-Akt signaling pathway was significantly enriched for OE-specific DEGs.…”