{"paper_id":"fa174044-7ad1-4cde-84d4-a53c79f5eaed","body_text":"Abstract\nThe mechanism involved in the pathogenesis of endometriosis is poorly understood. The purpose of this study is to identify key deubiquitinating enzymes (DUBs) for endometriosis diagnosis and elucidate the possible mechanism, offering novel insights for noninvasive early diagnosis and treatment. Four gene expression datasets were employed from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) between endometriosis and normal controls. GO and KEGG pathways were performed for enrichment analysis. Calibration curves, ROC, DCA, and clinical impact curves verified the clinical usefulness of the nomogram model. In addition, the ssGSEA method was conducted to estimate 23 types of immune cells. A specific DUB gene signature was constructed with Lasso regression, univariate logistic regression, and SVM analysis. RT-qPCR validated the expression of biomarkers. A total of 85 endometriosis-related DUBs were identified in the eutopic endometrium. Among them, 20 DUBs were found to be correlated with the severity of endometriosis. A diagnostic risk model based on five DUB-related genes (USP21, USP48, ZRANB1, COPS5, and EIF3F) was developed using lasso-cox regression analysis. The nomogram model exhibited a strong predictive ability to diagnose endometriosis. KEGG analysis revealed that ubiquitin-mediated proteolysis was activated in patients suffering from severe symptoms. Analysis of immune cell infiltration revealed a positive correlation between USP21 and multiple immune cells in the eutopic endometrium. However, EIF3F showed an opposite relationship. Dysregulation of DUBs was related to the immune microenvironment in endometriosis. Results from RT-qPCR confirmed the expression of DEGs in clinical samples. In summary, the diagnostic model for endometriosis constructed using five differentially expressed DUB genes demonstrates strong diagnostic capability, suggesting that these genes could serve as potential candidate biomarkers and therapeutic targets.\nSimilar content being viewed by others\nData Availability\nThe data used to support the findings of this study are available from the corresponding author upon request.\nReferences\nAgarwal SK et al (2019) Clinical diagnosis of endometriosis: a call to action. Am J Obstet Gynecol 220:354 e351-354 e312. https://doi.org/10.1016/j.ajog.2018.12.039\nAn T et al (2022) Insights into the properties, biological functions, and regulation of USP21. Front Pharmacol 13:944089. https://doi.org/10.3389/fphar.2022.944089\nBaek KH et al (2020) Cellular functions of OCT-3/4 regulated by ubiquitination in proliferating cells. 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Asia Pac J Clin Oncol 17:471–477. https://doi.org/10.1111/ajco.13480\nZhu Y et al (2019) Trabid inhibits hepatocellular carcinoma growth and metastasis by cleaving RNF8-induced K63 ubiquitination of Twist1. Cell Death Differ 26:306–320. https://doi.org/10.1038/s41418-018-0119-2\nAcknowledgements\nThe authors are grateful to Hongcun Bao for the assistance in project design and statistical analysis for this study.\nFunding\nGrant support was provided by the Zhejiang Provincial Medical and Health Technology Plan (2022RC236, 2023KY205); Zhejiang Provincial Natural Science Foundation of China (Q24H040012); Foundation of Zhejiang Provincial Education Department (Y202351214); Administration of Traditional Chinese Medicine of Zhejiang Province, China(2024ZL740).\nAuthor information\nAuthors and Affiliations\nContributions\nXYY and KY contributed to the material preparation, data collection, and analysis. QTZ and HC conducted experiments. XYY and LLZ prepared the diagrams and drafted the manuscript. CZP and LLZ conceived and designed the research, and reviewed the manuscript.\nCorresponding authors\nEthics declarations\nConflict of interest\nThe authors declare no conflicts of interest.\nEthical Approval\nThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Women’s Hospital, Zhejiang University School of Medicine (IRB-20230278-R).\nConsent to Participate\nInformed consent was obtained from all individual participants included in the study.\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\nYang, X., Yan, K., Zhan, Q. et al. Exploration of Diagnostic Deubiquitinating Enzymes in Endometriosis and Its Immune Infiltration. Biochem Genet 62, 4359–4379 (2024). https://doi.org/10.1007/s10528-023-10653-w\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s10528-023-10653-w","source_license":"CC0","license_restricted":false}