{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T03:16:48Z","timestamp":1780370208371,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":351,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"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":["BioMed Research International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endometriosis is a chronic gynecological disorder characterized by the presence of endometrial\u2010like tissue outside the uterine cavity, causing chronic pain and infertility. Hypoxia plays a significant role in the progression of endometriosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed bioinformatics analysis on GEO datasets to identify differentially expressed genes (DEGs) in endometriosis, using weighted gene coexpression network analysis (WGCNA)and GeneCards for hypoxia\u2010related genes. Machine learning models identified key hub genes. CCK\u20108, EdU, and Transwell assays assessed cell proliferation, migration, and invasion. Molecular docking was performed to investigate the interactions between the drug and the protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the GEO dataset analysis, 2834 DEGs were identified. Using WGCNA, a green module strongly correlated with endometriosis was identified. Intersecting this module with the hypoxia\u2010related genes resulted in the selection of 449 key genes. Machine learning models, including support vector machines (SVMs), were employed to identify hypoxia\u2010related DEGs with significant predictive value. LASSO and SVM\u2010RFE were used to refine this list, ultimately selecting six hub genes: DDR2, ENO3, ESM1, NMBR, PRKAB1, and PRPF19. Validation with an independent dataset confirmed DDR2 as a promising diagnostic biomarker. Functional assays demonstrated that DDR2 knockdown significantly inhibited cell proliferation, migration, and invasion in the endometriosis cell lines VK2\/E6E7 and 12Z. DDR2, a receptor tyrosine kinase, mediates extracellular matrix remodeling and cell invasion under hypoxia. By interacting with collagen and HIFs, DDR2 activates pathways that promote MMP secretion, angiogenesis, and migration, facilitating endometriotic cell progression in the hypoxic microenvironment. Molecular docking identified key amino acids near DDR2\u2032s binding pocket that form hydrophobic interactions, hydrogen bonds, and\n                      <jats:italic>\u03c0<\/jats:italic>\n                      \u2010stacking with baicalein, cavidine, sitogluside, and stigmasterol, further supporting DDR2\u2032s potential as a therapeutic target.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DDR2 is a key hypoxia\u2010related gene in endometriosis and a promising diagnostic and therapeutic biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/bmri\/4765791","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:32:47Z","timestamp":1766122367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bioinformatics Analysis of Hypoxia\u2010Related Mechanisms in Endometriosis: DDR2 as a Potential Diagnostic and Therapeutic Biomarker"],"prefix":"10.1155","volume":"2025","author":[{"given":"Mingqi","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-6776","authenticated-orcid":false,"given":"Xiaoqin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.14817.1"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2022-070750"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/6.1.37"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1490"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew293"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.255"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054254"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.879015"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2016.02.036"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12522-009-0031-z"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19071852"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/179515"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgt209"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2015.50"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2018.03.004"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2015.1121225"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.2174\/0118761429315431240712100124"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.10R25FM"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389201022666210224130022"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2010.05.003"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew081"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-03227"},{"key":"e_1_2_13_23_2","first-page":"399","article-title":"Hypoxia Responsive miR-210 Promotes Cell Survival and Autophagy of Endometriotic Cells in Hypoxia","volume":"20","author":"Xu T. 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