Meihong Chen1, Yilu Zhou2,3, Hong Xu4, Charlotte Hill2, Rob M Ewing2,3, Deming He1, Xiaoling Zhang5, Yihua Wang6,7,8. 1. Department of Gynecology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. 2. Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK. 3. Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK. 4. Department of Medicine, Nanchang University, Nanchang, Jiangxi, China. 5. Department of Gynecology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. xlzzz777@126.com. 6. Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK. yihua.wang@soton.ac.uk. 7. Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK. yihua.wang@soton.ac.uk. 8. NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, SO16 6YD, UK. yihua.wang@soton.ac.uk.
Abstract
BACKGROUND: Endometriosis is a frequently occurring disease in women, which seriously affects their quality of life. However, its etiology and pathogenesis are still unclear. METHODS: To identify key genes/pathways involved in the pathogenesis of endometriosis, we recruited 3 raw microarray datasets (GSE11691, GSE7305, and GSE12768) from Gene Expression Omnibus database (GEO), which contain endometriosis tissues and normal endometrial tissues. We then performed in-depth bioinformatic analysis to determine differentially expressed genes (DEGs), followed by gene ontology (GO), Hallmark pathway enrichment and protein-protein interaction (PPI) network analysis. The findings were further validated by immunohistochemistry (IHC) staining in endometrial tissues from endometriosis or control patients. RESULTS: We identified 186 DEGs, of which 118 were up-regulated and 68 were down-regulated. The most enriched DEGs in GO functional analysis were mainly associated with cell adhesion, inflammatory response, and extracellular exosome. We found that epithelial-mesenchymal transition (EMT) ranked first in the Hallmark pathway enrichment. EMT may potentially be induced by inflammatory cytokines such as CXCL12. IHC confirmed the down-regulation of E-cadherin (CDH1) and up-regulation of CXCL12 in endometriosis tissues. CONCLUSIONS: Utilizing bioinformatics and patient samples, we provide evidence of EMT in endometriosis. Elucidating the role of EMT will improve the understanding of the molecular mechanisms involved in the development of endometriosis.
BACKGROUND: Endometriosis is a frequently occurring disease in women, which seriously affects their quality of life. However, its etiology and pathogenesis are still unclear. METHODS: To identify key genes/pathways involved in the pathogenesis of endometriosis, we recruited 3 raw microarray datasets (GSE11691, GSE7305, and GSE12768) from Gene Expression Omnibus database (GEO), which contain endometriosis tissues and normal endometrial tissues. We then performed in-depth bioinformatic analysis to determine differentially expressed genes (DEGs), followed by gene ontology (GO), Hallmark pathway enrichment and protein-protein interaction (PPI) network analysis. The findings were further validated by immunohistochemistry (IHC) staining in endometrial tissues from endometriosis or control patients. RESULTS: We identified 186 DEGs, of which 118 were up-regulated and 68 were down-regulated. The most enriched DEGs in GO functional analysis were mainly associated with cell adhesion, inflammatory response, and extracellular exosome. We found that epithelial-mesenchymal transition (EMT) ranked first in the Hallmark pathway enrichment. EMT may potentially be induced by inflammatory cytokines such as CXCL12. IHC confirmed the down-regulation of E-cadherin (CDH1) and up-regulation of CXCL12 in endometriosis tissues. CONCLUSIONS: Utilizing bioinformatics and patient samples, we provide evidence of EMT in endometriosis. Elucidating the role of EMT will improve the understanding of the molecular mechanisms involved in the development of endometriosis.
Authors: Neil P Johnson; Lone Hummelshoj; G David Adamson; Jörg Keckstein; Hugh S Taylor; Mauricio S Abrao; Deborah Bush; Ludwig Kiesel; Rulla Tamimi; Kathy L Sharpe-Timms; Luk Rombauts; Linda C Giudice Journal: Hum Reprod Date: 2016-12-05 Impact factor: 6.918
Authors: M Louise Hull; Claudia Rangel Escareno; Jane M Godsland; John R Doig; Claire M Johnson; Stephen C Phillips; Stephen K Smith; Simon Tavaré; Cristin G Print; D Stephen Charnock-Jones Journal: Am J Pathol Date: 2008-08-07 Impact factor: 4.307
Authors: Aniko Hever; Richard B Roth; Peter Hevezi; Maria E Marin; Jose A Acosta; Hector Acosta; Jose Rojas; Rosa Herrera; Dimitri Grigoriadis; Evan White; Paul J Conlon; Richard A Maki; Albert Zlotnik Journal: Proc Natl Acad Sci U S A Date: 2007-07-17 Impact factor: 11.205