New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis

BackgroundFerroptosis, a recently discovered iron-dependent cell death, is linked to various diseases but its role in endometriosis is still not fully understood.MethodsIn this study, we integrated microarray data of endometriosis from the GEO database and ferroptosis-related genes (FRGs) from the F...

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Main Authors: Lusha Liu, Feifei Han, Naiyi Du, Yakun Liu, Aihong Duan, Shan Kang, Bin Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507083/full
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author Lusha Liu
Feifei Han
Naiyi Du
Yakun Liu
Aihong Duan
Shan Kang
Bin Li
author_facet Lusha Liu
Feifei Han
Naiyi Du
Yakun Liu
Aihong Duan
Shan Kang
Bin Li
author_sort Lusha Liu
collection DOAJ
description BackgroundFerroptosis, a recently discovered iron-dependent cell death, is linked to various diseases but its role in endometriosis is still not fully understood.MethodsIn this study, we integrated microarray data of endometriosis from the GEO database and ferroptosis-related genes (FRGs) from the FerrDb database to further investigate the regulation of ferroptosis in endometriosis and its impact on the immune microenvironment. WGCNA identified ferroptosis-related modules, annotated by GO & KEGG. MNC algorithm pinpointed hub FRGs. Cytoscape construct a ceRNA network, and ROC curves evaluated diagnostic efficacy of hub FRGs. Consensus cluster analysis identified ferroptosis subclusters, and CIBERSORT assessed immune infiltration of these subclusters. Finally, RT-qPCR validated hub FRG expression in clinical tissues.ResultsWe identified two ferroptosis modules of endometriosis, and by enrichment analysis, they are closely linked with autophagy, mTOR, oxidative stress, and FOXO pathways. Furthermore, we identified 10 hub FRGs, and the ROC curve showed better predictive ability for diagnosing. RT-qPCR confirmed that the tissue expression of 10 hub FRGs was mostly consistent with the database results. Subsequently, we developed a ceRNA network based on 4 FRGs (BECN1, OSBPL9, TGFBR1, GSK3B). Next, we identified two ferroptosis subclusters of endometriosis and discovered that they are closely linked with endometriosis stage. Importantly, immune enrichment analysis illustrated that the expression levels of immune cells and immune checkpoint genes were significantly different in the two ferroptosis subclusters. Specifically, the ferroptosis subcluster with stage III-IV of endometriosis is more inclined to the immunosuppressive microenvironment.ConclusionsOur study showed that ferroptosis may jointly promote endometriosis progression by remodeling the immune microenvironment, offering new insights into pathogenesis and therapeutics.
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spelling doaj-art-0cd2f2b60745408384d6ba31ea172ac82025-01-13T05:10:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15070831507083New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysisLusha Liu0Feifei Han1Naiyi Du2Yakun Liu3Aihong Duan4Shan Kang5Bin Li6Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Gynecology, Handan Central Hospital, Handan, ChinaDepartment of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Gynecology, Handan Central Hospital, Handan, ChinaDepartment of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Gynecology, Handan Central Hospital, Handan, ChinaBackgroundFerroptosis, a recently discovered iron-dependent cell death, is linked to various diseases but its role in endometriosis is still not fully understood.MethodsIn this study, we integrated microarray data of endometriosis from the GEO database and ferroptosis-related genes (FRGs) from the FerrDb database to further investigate the regulation of ferroptosis in endometriosis and its impact on the immune microenvironment. WGCNA identified ferroptosis-related modules, annotated by GO & KEGG. MNC algorithm pinpointed hub FRGs. Cytoscape construct a ceRNA network, and ROC curves evaluated diagnostic efficacy of hub FRGs. Consensus cluster analysis identified ferroptosis subclusters, and CIBERSORT assessed immune infiltration of these subclusters. Finally, RT-qPCR validated hub FRG expression in clinical tissues.ResultsWe identified two ferroptosis modules of endometriosis, and by enrichment analysis, they are closely linked with autophagy, mTOR, oxidative stress, and FOXO pathways. Furthermore, we identified 10 hub FRGs, and the ROC curve showed better predictive ability for diagnosing. RT-qPCR confirmed that the tissue expression of 10 hub FRGs was mostly consistent with the database results. Subsequently, we developed a ceRNA network based on 4 FRGs (BECN1, OSBPL9, TGFBR1, GSK3B). Next, we identified two ferroptosis subclusters of endometriosis and discovered that they are closely linked with endometriosis stage. Importantly, immune enrichment analysis illustrated that the expression levels of immune cells and immune checkpoint genes were significantly different in the two ferroptosis subclusters. Specifically, the ferroptosis subcluster with stage III-IV of endometriosis is more inclined to the immunosuppressive microenvironment.ConclusionsOur study showed that ferroptosis may jointly promote endometriosis progression by remodeling the immune microenvironment, offering new insights into pathogenesis and therapeutics.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507083/fullferroptosisendometriosisWGCNAimmune infiltrationimmune checkpoint genes
spellingShingle Lusha Liu
Feifei Han
Naiyi Du
Yakun Liu
Aihong Duan
Shan Kang
Bin Li
New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis
Frontiers in Immunology
ferroptosis
endometriosis
WGCNA
immune infiltration
immune checkpoint genes
title New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis
title_full New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis
title_fullStr New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis
title_full_unstemmed New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis
title_short New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis
title_sort new insights into the ferroptosis and immune infiltration in endometriosis a bioinformatics based analysis
topic ferroptosis
endometriosis
WGCNA
immune infiltration
immune checkpoint genes
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507083/full
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