{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:15:47Z","timestamp":1790802947277,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":33,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460304"],"award-info":[{"award-number":["82460304"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endometriosis (EM) is associated with immune dysregulation, while dysfunction of natural killer (NK) cells is regarded as a key mechanism underlying immune escape and the persistent growth of ectopic lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>This study used single\u2010cell RNA sequencing (scRNA\u2010seq) on lesions from three patients with EM and on three normal endometrium samples and integrated these data with three bulk RNA\u2010seq datasets from GEO (GSE105765, GSE7305, and GSE6364). Seurat, Monocle, limma, least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature elimination (SVM\u2010RFE) were used for cell clustering, trajectory inference, differential expression analysis, and feature selection. Immune\u2010cell composition and pathway activity were evaluated with CIBERSORT and GSVA. Gene expression was validated by qPCR, and cell migration and invasiveness were assessed using wound healing and Transwell assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      scRNA\u2010seq resolved 11 clusters assigned to eight major cell types. By integrating pseudotime features with bulk data, 20 differentially expressed genes (DEGs) were prioritized, and machine\u2010learning analyses identified three key genes: granulysin (GNLY), perforin 1 (PRF1), and ENTPD1. The three\u2010gene model showed good discrimination in the training set and two external validation cohorts (AUCs 0.84, 0.67, and 0.77, respectively). GNLY and PRF1 were predominantly expressed in NK cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and correlated with activation signatures, whereas ENTPD1 was highly expressed in endometrial stromal cells and enhanced their migratory and invasive capacities. ENTPD1 may contribute to disease via adenosine signaling\u2013mediated modulation of NK\u2013cell function. In silico analyses also nominated candidate agents targeting this pathway, including resveratrol, ibuprofen, and danazol.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study highlights the central role of NK\u2013cell dysfunction in EM pathogenesis and proposes GNLY, PRF1, and ENTPD1 as potential molecular diagnostic biomarkers. Notably, ENTPD1 appears to have dual functions, including immunomodulation and promotion of stromal cell migration, which promotes lesion formation. These findings provide a mechanistic rationale and actionable targets for earlier screening and targeted therapy in EM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/9028037","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T14:03:22Z","timestamp":1770127402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Single\u2010Cell Transcriptomics Reveals Biomarkers for NK Cell Dysfunction in Endometriosis\u2010Associated Immune Dysregulation"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8899-0672","authenticated-orcid":false,"given":"Wangshu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3706-393X","authenticated-orcid":false,"given":"Aziz","family":"ur Rehman Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3382-3759","authenticated-orcid":false,"given":"Xiaohui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6040-5448","authenticated-orcid":false,"given":"Daqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3648-8864","authenticated-orcid":false,"given":"Chunfang","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00242"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0008-5"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.12.039"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2018.06.001"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.07.004"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1530\/REP-08-0407"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000292720"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1582"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deq020"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2916070"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2016.04.289"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12577"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells14010058"},{"key":"e_1_2_12_14_2","first-page":"3112","article-title":"Ovarian Steroid Regulation of Vascular Endothelial Growth Factor in the Human Endometrium: Implications for Angiogenesis during the Menstrual Cycle and in the Pathogenesis of Endometriosis","volume":"81","author":"Shifren J. 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