{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:04:17Z","timestamp":1790053457748,"version":"4.0.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate Nectin-4 expression in primary and matched metastatic penile squamous cell carcinoma (PSCC) lesions and to assess its associations with clinicopathological features and survival outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 123 patients with pathologically confirmed PSCC treated at our hospital between 2018 and 2024. Nectin-4 expression was assessed by immunohistochemistry using the H-score (0-300) in primary tumors and 30 matched lymph node metastases, and associations with pathological features, paired primary-metastatic differences, and survival outcomes were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nectin-4 was widely expressed in PSCC. Higher Nectin-4 expression was observed in less aggressive tumors. Expression was higher in T1 than in T2 stage (95% CI 19.10-79.28; P &amp;lt; 0.01) and decreased from G1 to G3, with significant differences between G1 and G2 (95% CI 0.39-63.83; P\u00a0=\u00a00.047) and between G1 and G3 (95% CI 24.41-170.43; P\u00a0=\u00a00.009). Expression in primary tumors was not significantly associated with nodal status. In paired samples, lymph node metastases showed lower H-scores than their matched primary tumors (95% CI 3.52-72.82; P\u00a0=\u00a00.032). Low Nectin-4 expression was associated with shorter overall survival in Kaplan-Meier and univariable Cox analyses, but it was not independently associated with survival after multivariable adjustment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Nectin-4 expression in PSCC is higher in early, better-differentiated tumors and lower in lymph node metastases. Low Nectin-4 expression was associated with poorer overall survival, although it was not an independent prognostic factor. These findings suggest that Nectin-4 may have prognostic relevance and potential value as a therapeutic target in PSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1912533","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:22:50Z","timestamp":1790050970000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced Nectin-4 expression in lymph node metastases of penile squamous cell carcinoma: a paired primary\u2013metastatic analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Tianhao","family":"Ma","sequence":"first","affiliation":[{"name":"Key Laboratory of Cancer Prevention and Therapy, Department of Urologic Oncology, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cancer Prevention and Therapy, Department of Urologic Oncology, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiran","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cancer Prevention and Therapy, Department of Urologic Oncology, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongcheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cancer Prevention and Therapy, Department of Urologic Oncology, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunsen","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cancer Prevention and Therapy, Department of Urologic Oncology, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cancer Prevention and Therapy, Department of Urologic Oncology, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cancer Prevention and Therapy, Department of Urologic Oncology, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00246-5","article-title":"Penile cancer","volume":"7","author":"Thomas","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J 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