{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:10:00Z","timestamp":1792271400104,"version":"4.4.0"},"reference-count":30,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["110-N5031"],"award-info":[{"award-number":["110-N5031"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["114-M0008"],"award-info":[{"award-number":["114-M0008"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["MQ5955"],"award-info":[{"award-number":["MQ5955"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Nectin-4 is a key therapeutic target of antibody\u2013drug conjugates (ADCs) in advanced urothelial carcinoma (UC), but its expression patterns and underlying biology across anatomical sites remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>This study aimed to elucidate Nectin-4-related features in bladder (urinary bladder carcinoma, UBC) and upper urinary tract (upper tract urothelial carcinoma, UTUC) through a multi-layered approach, including primary tumor characterization, paired primary\u2013metastatic analyses, and immune transcriptomic profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>A retrospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed primary tumors from 139 patients with advanced UC, including 56 with paired metastatic specimens and 75 with sufficient primary tumor tissue for immune profiling. Membranous Nectin-4 expression was assessed by immunohistochemistry and categorized as Nectin-4\n                      <jats:sup>High<\/jats:sup>\n                      (H-score 100\u2013300) or Nectin-4\n                      <jats:sup>Low<\/jats:sup>\n                      (0\u201399). Immune profiling was performed using the nCounter\n                      <jats:sup>\u00ae<\/jats:sup>\n                      PanCancer Immune Profiling Panel (NanoString Technologies). External transcriptomic datasets (UBC: TCGA-BLCA; UTUC: GSE244957) were used to assess the consistency of immune profiling results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Primary UBC tumors exhibited significantly higher Nectin-4 expression than UTUC tumors (median H-score 150.0 vs 95.0,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.005; Nectin-4\n                      <jats:sup>High<\/jats:sup>\n                      70.6% vs 50.0%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.018). Among paired specimens, 33.9% (19\/56) showed primary\u2013metastatic changes in Nectin-4 status, which occurred more frequently in UBC than in UTUC (52.2% vs 21.2%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.017). Immune profiling revealed a relatively immune-depleted pattern in Nectin-4\n                      <jats:sup>High<\/jats:sup>\n                      versus Nectin-4\n                      <jats:sup>Low<\/jats:sup>\n                      tumors in UBC, whereas this pattern was less evident in UTUC. These findings were consistent with those from external transcriptomic datasets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>UBC and UTUC demonstrate distinct Nectin-4 expression patterns and associated immune contexture, highlighting the biological heterogeneity of Nectin-4 in advanced UC. Further prospective studies are warranted to validate these findings and clarify their clinical implications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359261463147","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:49:06Z","timestamp":1783421346000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Site-specific differences in Nectin-4 expression and associated immune contexture in advanced urothelial carcinoma: implications for Nectin-4-targeted ADCs"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6484-0090","authenticated-orcid":false,"given":"Fu-Jen","family":"Hsueh","sequence":"first","affiliation":[{"name":"Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan"},{"name":"Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0108-240X","authenticated-orcid":false,"given":"Chung-Chieh","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-8045","authenticated-orcid":false,"given":"Chia-Lang","family":"Hsu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan"},{"name":"Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan"},{"name":"Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5534-9124","authenticated-orcid":false,"given":"Shu-Cheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan"},{"name":"Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6689-9640","authenticated-orcid":false,"given":"Jhe-Cyuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan"},{"name":"Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-0340","authenticated-orcid":false,"given":"Chien-Huai","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan"},{"name":"Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan"},{"name":"Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Chieh","family":"Chueh","sequence":"additional","affiliation":[{"name":"Department of Urology, National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-7655","authenticated-orcid":false,"given":"Yu-Chieh","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Oncology, National Taiwan University 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