{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:07:45Z","timestamp":1777950465094,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":123,"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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Genomics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ovarian cancer is characterized by high mortality, extensive genomic instability driven by copy number alterations, and a highly immunosuppressive tumor microenvironment. Increasing evidence suggests that chronic inflammation and stromal\u2013immune interactions contribute to tumor progression and therapeutic resistance. Bradykinin receptor B1 (BDKRB1), an inflammation\u2010inducible G protein\u2013coupled receptor, has been implicated in tumor\u2010associated inflammatory signaling; however, its genomic determinants and immunological relevance in ovarian cancer remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an integrative multiomics analysis of BDKRB1 using TCGA\u2010OV and multiple independent GEO cohorts. The analytical framework incorporated bulk transcriptomics, copy number variation profiling, single\u2010cell RNA sequencing, immune cell deconvolution, pathway enrichment analysis (GSEA, GSVA, and PROGENy), and pharmacogenomic modeling. Patients were dichotomized into BDKRB1\u2010high and BDKRB1\u2010low groups using cohort\u2010specific median expression to ensure cross\u2010dataset consistency. Associations with genomic instability, TME features, and drug response patterns were systematically evaluated. Quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) was further performed to validate BDKRB1 expression in ovarian cancer cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BDKRB1 was consistently overexpressed in ovarian cancer and associated with unfavorable clinical outcomes across multiple cohorts. Elevated BDKRB1 expression correlated with increased genomic instability, reflected by higher fractions of the genome altered, gained, and lost. Although copy number variation partially explained BDKRB1 upregulation, the modest correlation suggested additional regulatory mechanisms. Tumors with high BDKRB1 expression exhibited immunosuppressive microenvironmental features, including enrichment of cancer\u2010associated fibroblasts and reduced estimated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell infiltration, despite concurrent activation of inflammatory signaling pathways. Single\u2010cell transcriptomic analysis further identified fibroblasts as a major cellular source of BDKRB1 expression. Functional analyses indicated associations between BDKRB1 and inflammatory signaling, metabolic pathways, and oncogenic programs. Pharmacogenomic analyses suggested distinct drug sensitivity patterns in BDKRB1\u2010high tumors and identified fasudil as a potential candidate compound for reversing BDKRB1\u2010associated transcriptional signatures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This integrative analysis identifies BDKRB1 as a microenvironment\u2010associated marker linking genomic instability with inflammatory and immunosuppressive tumor ecosystems in ovarian cancer. Although the findings are primarily associative, they provide a systems\u2010level perspective on immune evasion mechanisms and highlight BDKRB1 as a potential biomarker for TME characterization and therapeutic hypothesis generation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijog\/2966274","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:27:14Z","timestamp":1777879634000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BDKRB1 Links Copy Number\u2013Defined Genomic Instability to Inflammatory and Immunosuppressive Tumor Ecosystems in Ovarian Cancer: An Integrative Multiomics Analysis"],"prefix":"10.1155","volume":"2026","author":[{"given":"Dali","family":"Pu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huagui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3432-9998","authenticated-orcid":false,"given":"Shan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21456"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06084-5"},{"key":"e_1_2_13_3_2","doi-asserted-by":"crossref","unstructured":"YangL. Molecular Mechanisms of Platinum-Based Chemotherapy Resistance in Ovar Ian Cancer Oncology Reports 47.","DOI":"10.3892\/or.2022.8293"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-17-0336"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911361"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21559"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-13-549"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-1130-z"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043068"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030667"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.panca22-c070"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/4640563"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.052"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2021.100293"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa407"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac959"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab003"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107468"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.7554\/elife.71880"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.034"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25432"},{"key":"e_1_2_13_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080898"},{"key":"e_1_2_13_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3984"},{"key":"e_1_2_13_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-011-9340-x"},{"key":"e_1_2_13_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00641-0"},{"key":"e_1_2_13_27_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2012.1475"},{"key":"e_1_2_13_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.872991"},{"key":"e_1_2_13_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.5945"},{"key":"e_1_2_13_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.02.003"},{"key":"e_1_2_13_31_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.9.11.11634"},{"key":"e_1_2_13_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-010-9468-5"},{"key":"e_1_2_13_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-13-11"}],"container-title":["International Journal of Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijog\/2966274","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/ijog\/2966274","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijog\/2966274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:27:16Z","timestamp":1777879636000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/ijog\/2966274"}},"subtitle":[],"editor":[{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/ijog\/2966274"],"URL":"https:\/\/doi.org\/10.1155\/ijog\/2966274","archive":["Portico"],"relation":{},"ISSN":["2314-436X","2314-4378"],"issn-type":[{"value":"2314-436X","type":"print"},{"value":"2314-4378","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2966274"}}