{"paper_id":"c3112b44-feb0-4d11-9339-521571c09205","body_text":"Abstract\nBackground\nPatients of ovary endometriosis have an abnormal immune micro-environment, leading to endometrial tissue that from retrograde menstruation evade immune surveillance and subsequently develop into ectopic lesions.\nObjective\nThis study aims to elucidate the crucial immune cells and molecular pathways that are associated with an aberrant immune micro-environment of endometriosis.\nMethod\nIn this study, we identified differentially expressed genes between ovarian ectopic endometrial tissue (OVE) and eutopic endometrial tissue from patients with endometriosis (PE) and non-endometriosis patients (CON) by analyzing the mRNA sequencing data. Additionally, we used WGCNA(Weighted Gene Co-expression Network Analysis) to screen for key genes related to immune cell infiltration and compared the sub-types of infiltrating immune cells using CIBERSORT(cell-type identification by estimating relative subsets of RNA transcript). Subsequently, we conducted a single-cell analysis on the identified key genes. Furthermore, we analyzed potential drugs suitable for ovarian endometriosis treatment using pRRophertic.\nResults\nSeven key genes associated with immune cell infiltration were screened out. The expression of these genes in OVE was significantly lower than that in PE and CON. These key genes were mainly enriched in the NK cell-mediated cytotoxicity pathway, especially for CD16 + CD56dim NK. Moreover, NK cells infiltration in ovarian endometriosis was significantly reduced compared with PE and CON, while M2 macrophage shown the opposite. Results of the single-cell analysis showed that the expression of the seven key genes in NK cells and monocyte-macrophages in OVE was significantly lower than that in PE or CON. Additionally, we identified potential drugs suitable for ovarian endometriosis treatment.\nConclusion\nThe decreased infiltration of NK cells and increased infiltration of M2 macrophages contribute to the evasion of immune surveillance against endometrial tissue, promoting the progression of OVE. Therefore, potential strategies for the treatment of OVE include increasing NK cell activation and decreasing M2 macrophage polarization.\nSimilar content being viewed by others\nReferences\nArtemova D, Vishnyakova P, Khashchenko E et al (2021) Endometriosis and cancer: exploring the role of macrophages. 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N Engl JMed 382:1244–1256\nFunding\nThis study was supported by the grants from the National Natural Science Foundation of China (Grant no.: 82301856) and Guangdong Medical Science and Technology Research Fund (Grant no.: B2023145).\nAuthor information\nAuthors and Affiliations\nCorresponding authors\nEthics declarations\nConflict of interest\nAll the authors certify that there is no potential conflicts of interest with any financial or organization regarding manuscript.\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nSupplementary Information\nBelow is the link to the electronic supplementary material.\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\nQuan, Q., Gu, H., Wang, Y. et al. Immune micro-environment analysis and drug screening for ovarian endometriosis. Genes Genom 46, 803–815 (2024). https://doi.org/10.1007/s13258-024-01497-8\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s13258-024-01497-8","source_license":"public-domain-us","license_restricted":false}