{"paper_id":"5a709958-7c76-4070-b2ca-9deaba21a391","body_text":"Abstract\nBackground\nEndometriosis is one of the chronic and prevalent diseases among women. There is limited knowledge about its pathophysiology at the cellular and molecular levels, causing a lack of a definite cure for this disease. In this study, differentially expressed genes (DEGs) between ectopic and paired eutopic endometrium in women with endometriosis were analyzed through bioinformatics analysis for better understanding of the molecular pathogenesis of endometriosis.\nMethods\nGene expression data of ectopic and paired eutopic endometrium were taken from the Gene Expression Omnibus database. DEGs were screened by the Limma package in R with considering specific criteria. Then, the protein–protein interaction network was reconstructed between DEGs. The fast unfolding clustering algorithm was used to find sub-networks (modules). Finally, the three most relevant modules were selected and the functional and pathway enrichment analyses were performed for the selected modules.\nResults\nA total of 380 DEGs (245 up-regulated and 135 down-regulated) were identified in the ectopic endometrium and compared with paired eutopic endometrium. The DEGs were predominantly enriched in an ensemble of genes encoding the extracellular matrix and associated proteins, metabolic pathways, cell adhesions and the innate immune system. Importantly, DPT, ASPN, CHRDL1, CSTA, HGD, MPZ, PED1A, and CLEC10A were identified as novel DEGs between the human ectopic tissue of endometrium and its paired eutopic endometrium.\nConclusion\nThe results of this study can open up a new window to better understanding of the molecular pathogenesis of endometriosis and can be considered for designing new treatment modalities.\nSimilar content being viewed by others\nReferences\nNamazi M, Behboodi Moghadam Z, Zareiyan A, Jafarabadi M. Impact of endometriosis on reproductive health: an integrative review. J Obstet Gynaecol. 2021;41(8):1183–91.\nClemenza S, Sorbi F, Noci I, Capezzuoli T, Turrini I, Carriero C, et al. From pathogenesis to clinical practice: emerging medical treatments for endometriosis. Best Pract Res Clin Obstet Gynaecol. 2018;51:92–101.\nPoli-Neto OB, Meola J, Rosa-e-Silva JC, Tiezzi D. Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu. Sci Rep. 2020;10(1):1–17.\nZhao L, Gu C, Ye M, Zhang Z, Han W, Fan W, et al. Identification of global transcriptome abnormalities and potential biomarkers in eutopic endometria of women with endometriosis: a preliminary study. Biomed Rep. 2017;6(6):654–62.\nWang Y, Nicholes K, Shih I-M. The origin and pathogenesis of endometriosis. Annu Rev Pathol. 2020;15:71–95.\nTerzic M, Aimagambetova G, Kunz J, Bapayeva G, Aitbayeva B, Terzic S, et al. Molecular basis of endometriosis and endometrial cancer: current knowledge and future perspectives. Int J Mol Sci. 2021;22(17):9274.\nBaranov V, Malysheva O, Yarmolinskaya M. Pathogenomics of endometriosis development. Int J Mol Sci. 2018;19(7):1852.\nFeng X, Qi L, Xu X, Feng Y, Gong X, Aili A, et al. Analysis of differences in the transcriptomic profiles of eutopic and ectopic endometriums in women with ovarian endometriosis. PeerJ. 2021;9:e11045.\nMurakami K, Kotani Y, Nakai H, Matsumura N. Endometriosis-associated ovarian cancer: the origin and targeted therapy. Cancers. 2020;12(6):1676.\nHaghverdi L, Lun AT, Morgan MD, Marioni JC. Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors. Nat Biotechnol. 2018;36(5):421–7.\nDai FF, Bao AY, Luo B, Zeng ZH, Pu XL, Wang YQ, et al. Identification of differentially expressed genes and signaling pathways involved in endometriosis by integrated bioinformatics analysis. Exp Ther Med. 2020;19(1):264–72.\nMalik A, Qamar I, Waquar S. MON-026 Estradiol triggering extracellular matrix degradation leading signalling cascades succeeding a feedback loop as contributing factor to develop endometriosis in females of reproductive age. JES. 2020. https://doi.org/10.1210/jendso/bvaa046.1673.\nΖafrakas M, Κοtronis Κ, Papasozomenou P, Eskitzis P, Grimbizis G. Extracellular matrix metalloproteinases in the etiopathogenesis of endometriosis: a systematic review and critical appraisal. CEOG. 2020;47(2):147–53.\nUnamuno X, Gómez-Ambrosi J, Ramírez B, Rodríguez A, Becerril S, Valentí V, et al. Dermatopontin: a novel adipokine promoting adipose tissue extracellular matrix remodelling and inflammation in obesity. J Clin Med. 2020;9(4):1069.\nCook CD, Hill AS, Guo M, Stockdale L, Papps JP, Isaacson KB, et al. Local remodeling of synthetic extracellular matrix microenvironments by co-cultured endometrial epithelial and stromal cells enables long-term dynamic physiological function. Integr Biol. 2017;9(4):271–89.\nWang L, Wu H, Wang L, Zhang H, Lu J, Liang Z, et al. Asporin promotes pancreatic cancer cell invasion and migration by regulating the epithelial-to-mesenchymal transition (EMT) through both autocrine and paracrine mechanisms. Cancer Lett. 2017;398:24–36.\nLiu T, Li B, Zheng X-F, Jiang S-D, Zhou Z-Z, Xu W-N, et al. Chordin-like 1 improves osteogenesis of bone marrow mesenchymal stem cells through enhancing BMP4-SMAD pathway. Front Endocrinol. 2019;10:360.\nZhao F, Liu H, Wang N, Yu L, Wang A, Yi Y, et al. Exploring the role of Luman/CREB3 in regulating decidualization of mice endometrial stromal cells by comparative transcriptomics. BMC Genom. 2020;21(1):1–14.\nDietze R, Starzinski-Powitz A, Scheiner-Bobis G, Tinneberg H-R, Meinhold-Heerlein I, Konrad L. Lysophosphatidic acid triggers cathepsin B-mediated invasiveness of human endometriotic cells. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863(11):1369–77.\nGao S, Shi Z, Li X, Li W, Wang Y, Liu Z, et al. Fatostatin suppresses growth and enhances apoptosis by blocking SREBP-regulated metabolic pathways in endometrial carcinoma. Oncol Rep. 2018;39(4):1919–29.\nAscher DB, Spiga O, Sekelska M, Pires DE, Bernini A, Tiezzi M, et al. Homogentisate 1, 2-dioxygenase (HGD) gene variants, their analysis and genotype–phenotype correlations in the largest cohort of patients with AKU. Eur J Hum Genet. 2019;27(6):888–902.\nGibson DA, Simitsidellis I, Collins F, Saunders PT. Endometrial intracrinology: oestrogens, androgens and endometrial disorders. Int J Mol Sci. 2018;19(10):3276.\nGhanavatinejad F, Pourteymourfard-Tabrizi Z, Mahnam K, Doosti A, Mehri-Ghahfarrokhi A, Pourhadi M, et al. In silico and in vitro effects of the I30T mutation on myelin protein zero instability in the cell membrane. Cell Biol Int. 2020;44(2):671–83.\nSymons LK, Miller JE, Kay VR, Marks RM, Liblik K, Koti M, et al. The immunopathophysiology of endometriosis. Trends Mol Med. 2018;24(9):748–62.\nVallvé-Juanico J, Houshdaran S, Giudice LC. The endometrial immune environment of women with endometriosis. Hum Reprod Update. 2019;25(5):565–92.\nSohn JO, Seong SY, Kim HJ, Jo YM, Lee KH, Chung MK, et al. Alterations in intracellular Ca2+ levels in human endometrial stromal cells after decidualization. Biochem Biophys Res Commun. 2019;515(2):318–24.\nHe M, Han Y, Cai C, Liu P, Chen Y, Shen H, et al. CLEC10A is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in lung adenocarcinoma. J Cell Mol Med. 2021;25(7):3391–9.\nAcknowledgements\nWe thank Dr. Mohadeseh Zarei ghobadi (Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran) for assistance with methodology and for comments that greatly improved the manuscript.\nFunding\nNo funding.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nConflict of interest\nThe authors declare that they have no conflict of interest.\nEthical approval\nOur study was a bioinformatic analysis and involving information freely available in the public domain (GEO database). The analysis of online datasets, from an open source, where the data are properly anonymized and informed consent was obtained at the time of original data collection, do not require ethical approval.\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nSepideh Abdollahi (MS) is a PhD candidate, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Dr. Pantea Izadi (PhD) is an Associate Professor, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Dr. Ghasem Azizi-Tabesh (PhD) is Reacher in Genomic Research center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nAbdollahi, S., Izadi, P. & Azizi-Tabesh, G. Bioinformatics Analysis Reveals Novel Differentially Expressed Genes Between Ectopic and Eutopic Endometrium in Women with Endometriosis. J Obstet Gynecol India 73 (Suppl 1), 115–123 (2023). https://doi.org/10.1007/s13224-023-01749-9\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s13224-023-01749-9","source_license":"CC0","license_restricted":false}