Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors—a network meta-analysis
BackgroundMolecular events that drive endometriosis (EM) and cause accompanying immune deregulation remain elusive. Our purpose was to identify key pathways involved in lesion formation across diverse populations and to detect transcriptomic changes in eutopic endometrium that accompany EM.MethodsWe...
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Frontiers Media S.A.
2025-07-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1619434/full |
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| author | Monika Golinska Monika Golinska Aleksander Rycerz Matylda Sobczak Jedrzej Chrzanowski Konrad Stawiski Wojciech Fendler Wojciech Fendler Wojciech Fendler |
| author_facet | Monika Golinska Monika Golinska Aleksander Rycerz Matylda Sobczak Jedrzej Chrzanowski Konrad Stawiski Wojciech Fendler Wojciech Fendler Wojciech Fendler |
| author_sort | Monika Golinska |
| collection | DOAJ |
| description | BackgroundMolecular events that drive endometriosis (EM) and cause accompanying immune deregulation remain elusive. Our purpose was to identify key pathways involved in lesion formation across diverse populations and to detect transcriptomic changes in eutopic endometrium that accompany EM.MethodsWe searched Gene Expression Omnibus and ArrayExpress and performed differential gene expression analysis and a network meta-analysis on nine qualifying datasets. Those contained transcriptomic data on 114 ectopic endometrium samples (EL), 138 eutopic endometrium samples from women with endometriosis (EEM), and 79 eutopic endometrium samples from women without endometriosis (EH). Gene ontology and enrichment analysis were performed in DAVID, Metascape, and Cytoscape, and drug repurposing was done in CMap.ResultsEEM compared to EH upregulated CCL21 and downregulated BIRC3, CEL, and LEFTY1 genes (|log2FC| > 0.5, p < 0.05). EL showed increased expression of complement and serpin genes (EL vs. EEM: C7, logFC = 3.38, p < 0.0001; C3, logFC = 2.40, p < 0.0001; SERPINE1, logFC = 1.02, p < 0.05; SERPINE2, logFC = 1.54, p < 0.001) and mast cell markers (EL vs. EEM: CPA3, logFC = 1.54, p < 0.0001; KIT, logFC = 0.74, p < 0.001). Functional enrichment analysis highlighted complement and coagulation, inflammation, angiogenesis, and extracellular matrix remodeling as drivers of endometriosis. Pharmacogenomic analysis indicated Janus kinase (JAK), cyclin-dependent kinase (CDK), and topoisomerase inhibitors as therapy targets.ConclusionOur results suggest an interplay between complement and coagulation, mast cells, extracellular matrix remodeling, and the JAK/STAT3 pathway in endometriosis. We underscore the significance of complement C3 and propose JAK inhibitors as therapy candidates. Detected expression differences between EEM and EH are important for the development of diagnosis via endometrial biopsy. |
| format | Article |
| id | doaj-art-ea636f19a6de45e2a5b06a680d2e6c9d |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-ea636f19a6de45e2a5b06a680d2e6c9d2025-07-08T05:26:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16194341619434Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors—a network meta-analysisMonika Golinska0Monika Golinska1Aleksander Rycerz2Matylda Sobczak3Jedrzej Chrzanowski4Konrad Stawiski5Wojciech Fendler6Wojciech Fendler7Wojciech Fendler8Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, PolandCancer Research UK Cambridge Institute (CRUK CI), University of Cambridge, Cambridge, United KingdomDepartment of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, PolandDepartment of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, PolandDepartment of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, PolandDepartment of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, PolandDepartment of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, PolandDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, United StatesMedical Research Agency, Warsaw, PolandBackgroundMolecular events that drive endometriosis (EM) and cause accompanying immune deregulation remain elusive. Our purpose was to identify key pathways involved in lesion formation across diverse populations and to detect transcriptomic changes in eutopic endometrium that accompany EM.MethodsWe searched Gene Expression Omnibus and ArrayExpress and performed differential gene expression analysis and a network meta-analysis on nine qualifying datasets. Those contained transcriptomic data on 114 ectopic endometrium samples (EL), 138 eutopic endometrium samples from women with endometriosis (EEM), and 79 eutopic endometrium samples from women without endometriosis (EH). Gene ontology and enrichment analysis were performed in DAVID, Metascape, and Cytoscape, and drug repurposing was done in CMap.ResultsEEM compared to EH upregulated CCL21 and downregulated BIRC3, CEL, and LEFTY1 genes (|log2FC| > 0.5, p < 0.05). EL showed increased expression of complement and serpin genes (EL vs. EEM: C7, logFC = 3.38, p < 0.0001; C3, logFC = 2.40, p < 0.0001; SERPINE1, logFC = 1.02, p < 0.05; SERPINE2, logFC = 1.54, p < 0.001) and mast cell markers (EL vs. EEM: CPA3, logFC = 1.54, p < 0.0001; KIT, logFC = 0.74, p < 0.001). Functional enrichment analysis highlighted complement and coagulation, inflammation, angiogenesis, and extracellular matrix remodeling as drivers of endometriosis. Pharmacogenomic analysis indicated Janus kinase (JAK), cyclin-dependent kinase (CDK), and topoisomerase inhibitors as therapy targets.ConclusionOur results suggest an interplay between complement and coagulation, mast cells, extracellular matrix remodeling, and the JAK/STAT3 pathway in endometriosis. We underscore the significance of complement C3 and propose JAK inhibitors as therapy candidates. Detected expression differences between EEM and EH are important for the development of diagnosis via endometrial biopsy.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1619434/fullendometriosiseutopic and ectopic endometriumnetwork meta-analysiscomplement and coagulationmast cellsJanus kinase (JAK) inhibitors |
| spellingShingle | Monika Golinska Monika Golinska Aleksander Rycerz Matylda Sobczak Jedrzej Chrzanowski Konrad Stawiski Wojciech Fendler Wojciech Fendler Wojciech Fendler Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors—a network meta-analysis Frontiers in Immunology endometriosis eutopic and ectopic endometrium network meta-analysis complement and coagulation mast cells Janus kinase (JAK) inhibitors |
| title | Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors—a network meta-analysis |
| title_full | Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors—a network meta-analysis |
| title_fullStr | Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors—a network meta-analysis |
| title_full_unstemmed | Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors—a network meta-analysis |
| title_short | Complement and coagulation cascade cross-talk in endometriosis and the potential of Janus Kinase inhibitors—a network meta-analysis |
| title_sort | complement and coagulation cascade cross talk in endometriosis and the potential of janus kinase inhibitors a network meta analysis |
| topic | endometriosis eutopic and ectopic endometrium network meta-analysis complement and coagulation mast cells Janus kinase (JAK) inhibitors |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1619434/full |
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