{"paper_id":"5ba6690a-4d71-40e2-bf41-1a9935bcc05f","body_text":"Abstract\nObjective\nTo identify differentially expressed genes (DEGs) in endometriosis and further analyze molecular mechanisms implicated in disease pathogenesis.\nMaterials and methods\nGene expression data (ID: GSE7846) of human endometrial endothelial cells (HEECs) collected from eutopic endometria tissue of patients with and without endometriosis were downloaded from Gene Expression Omnibus. DEGs were screened using Limma package, followed by enrichment analysis using clusterProfiler package in R. Thereafter, protein–protein interactions (PPIs) were analyzed using STRING (Search Tool for the Retrieval of Interacting Genes) database and visualized by Cytoscape software. Meanwhile, transcription factors were screened from the DEGs based on TRANSFA database, followed by construction of regulatory network using Cytoscape.\nResults\nA total of 2255 up- and 408 down-regulated genes were identified in endometriosis patients as compared with control patients. Those DEGs were predominantly enriched in focal adhesion (e.g., FN1, EGF, FYN, EGFR, RAC1, CCND1 and JUN), regulation of actin cytoskeleton (e.g., FN1, EGF, EGFR, RAC1 and JUN) and MAPK signaling pathway (e.g., EGF, EGFR, RAC1, JUN, TGFB1 and MYC). Importantly, EGF, EGFR, JUN, FN1, RAC1, TGFB1, CCND1 and FYN were hub nodes in the PPI network. Additionally, TGFB1, SMAD1 and SMAD4 showed up-regulation in TGFB signaling pathway. Transcription factor MYC had a regulatory effect on the most DEGs, including TGFB1, RAC1 and CCND1.\nConclusions\nFocal adhesion, regulation of actin cytoskeleton, MAPK and TGFB/SMAD signaling pathway may be important molecular mechanism underlying the pathogenesis of endometriosis.\nSimilar content being viewed by others\nReferences\nCramer DW, Missmer SA (2002) The epidemiology of endometriosis. Ann N Y Acad Sci 955(1):11–22\nKobayashi H, Kajihara H, Yamada Y, Tanase Y, Kanayama S, Furukawa N, Noguchi T, Haruta S, Yoshida S, Naruse K, Sado T, Oi H (2011) Risk of carcinoma in women with ovarian endometrioma. Front Biosci 3:529–539\nVercellini P, Vigano P, Somigliana E, Fedele L (2014) Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 10(5):261–275. doi:10.1038/nrendo.2013.255\nKobayashi H, Imanaka S, Nakamura H, Tsuji A (2014) Understanding the role of epigenomic, genomic and genetic alterations in the development of endometriosis (review). 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Fertil Steril 89(5):1069–1072\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nConflict of interest\nNone.\nRights and permissions\nAbout this article\nCite this article\nPing, S., Ma, C., Liu, P. et al. Molecular mechanisms underlying endometriosis pathogenesis revealed by bioinformatics analysis of microarray data. Arch Gynecol Obstet 293, 797–804 (2016). https://doi.org/10.1007/s00404-015-3875-y\nReceived:\nAccepted:\nPublished:\nIssue date:\nDOI: https://doi.org/10.1007/s00404-015-3875-y","source_license":"CC0","license_restricted":false}