{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:55:38Z","timestamp":1791262538138,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy. Ferroptosis, an iron\u2010dependent lipid peroxidation\u2010associated cell death mode, provides a new target for tumor therapy. Nevertheless, its impact on EOC tumorigenesis is not well defined. The quality control, dimensionality reduction, and EOC clustering for the gene expression data were performed through the Scanpy pipeline for single\u2010cell RNA sequence from GEO (GSE165897). Ferroptosis pathway scoring, computation of transcription factor activity, and analyzes for cell\u2013cell communication were conducted. An independent validation cohort (GSE300897,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919,002 cells) was analyzed to confirm ferroptosis signature robustness. Expression of ferroptosis\u2010related genes in SKOV3 and OVCAR3 cells was confirmed using RT\u2010qPCR and immunoassays after treatment with erastin, RSL3, and ferrostatin\u20101 rescue. NRF2 siRNA knockdown and co\u2010culture experiments were performed for functional validation. A total of 51,702 cells from 11 patients were analyzed and clustered into 18 clusters that included EOC cells (16.9%), immune cells (67.6%), and stromal cells (15.6%), encompassing 27 fine\u2010grained cell subtypes. KEGG enrichment revealed that ferroptosis, fatty acid metabolism, and glutathione metabolism were the major pathways. Transcription factor profiling indicated increased NRF2 activation in EOC cells, which implied an augmented ferroptosis\u2010resistance capacity. Signaling between cells also revealed three key ligand\u2010receptor interactions, SPP1\u2010CD44, VEGFA\u2010KDR, and CCL2\u2010CCR2, which are involved in the regulation of ferroptosis and were functionally validated in a triple co\u2010culture model. NRF2 siRNA knockdown synergistically enhanced erastin\u2010induced ferroptosis sensitization (C11\u2010BODIPY: 4.52\u2010fold), rescued by ferrostatin\u20101. Platinum\u2010refractory patients in GSE300897 showed significantly altered ferroptosis scores (Mann\u2013Whitney\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20093.22e\u201024), linking ferroptosis to clinical platinum sensitivity. Our work uncovers ferroptosis dysregulation as a key driver of EOC pathogenesis, with NRF2 being a master regulator of resistance to ferroptosis and suggesting new therapeutic approaches for ovarian cancer.\n                  <\/jats:p>","DOI":"10.1002\/cam4.72257","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:01:51Z","timestamp":1789102911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Transcriptomic Analysis Reveals Ferroptosis\u2010Related Signatures and Tumor Microenvironment Heterogeneity in Epithelial Ovarian Cancer"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6774-5923","authenticated-orcid":false,"given":"Jie","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Qingdao University Qingdao China"},{"name":"Department of Reproductive Medicine, Qingdao Hospital University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital) Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Qingdao Hospital University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital) Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxin","family":"Li","sequence":"additional","affiliation":[{"name":"Internal Medicine Department New Century Women's and Children's Hospital Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Qingdao University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21559"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3773"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14410"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00962-1"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020177"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.025"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2020.101417"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.010"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-020-00789-5"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.021"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-00462-0"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2298-2"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.11"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101107"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1714209"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.76"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-0521"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0926-0"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.5719"},{"key":"e_1_2_13_23_1","first-page":"69","article-title":"NRF2\u2010Mediated Regulation of Ferroptosis in Ovarian Cancer","volume":"525","author":"Seo J. 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