{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T23:46:07Z","timestamp":1761176767812,"version":"build-2065373602"},"reference-count":42,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prostate cancer is one of the principal malignancies threatening human health, and the development of castration resistance often constitutes a major cause of treatment failure in its management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To elucidate the potential association between programmed death\u2010ligand 1 (PD\u2010L1) and castration resistance in prostate cancer, we analyzed the expression levels of PD\u2010L1 in both primary prostate cancer tissues and castration\u2010resistant prostate cancer (CRPC) specimens as well as in corresponding cell lines by using western blots and immunohistochemistry. Then, we explored the specific mechanisms through transcriptomic sequencing technology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed that, compared to adjacent non\u2010cancerous tissue, PD\u2010L1 expression was unexpectedly lower in primary prostate cancer but notably elevated in CRPC tissues and cells. In CRPC cell lines where PD\u2010L1 was knocked down, a significant suppression of proliferation, invasion, and migration capabilities was observed. By employing next\u2010generation sequencing technology, we investigated the impact of PD\u2010L1 knockdown on intracellular signaling pathways in castration\u2010resistant cells. The results demonstrated that PD\u2010L1 knockdown led to alterations in gene expression within several signaling pathways, including those involved in cell surface interactions, regulation of natural killer cell activity, and sodium channel regulatory activity. We further elucidated through experimentation that PD\u2010L1 contributes to tumor progression in CRPC by modulating the expression of SCUBE1. More intriguingly, PD\u2010L1 knockdown also appeared to induce changes at the level of alternative splicing in multiple genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PD\u2010L1 is upregulated in CRPC and can modulate the expression of multiple tumor\u2010associated genes in CRPC cells. Finally, we found that PD\u2010L1 contributes to tumor progression in CRPC by modulating the expression of SCUBE1. This study provides a theoretical basis for understanding the intracellular signaling mediated by PD\u2010L1 and offers valuable insights into the mechanisms underlying castration resistance in prostate cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71225","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T09:49:59Z","timestamp":1757411399000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Functional Role of Programmed Death\u2010Ligand 1 (\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    ) in the Castration\u2010Resistant Prostate Cancer Using Transcriptomic Sequencing Analysis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6613-7718","authenticated-orcid":false,"given":"Lin","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Pathology First Affiliated Hospital Dalian Medical University  Dalian China"},{"name":"The Key Laboratory of Tumor Stem Cell Research of Liaoning Province Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology First Affiliated Hospital Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialin","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Pathology First Affiliated Hospital Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Mao","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Tumor Stem Cell Research of Liaoning Province Dalian Medical University  Dalian China"},{"name":"Department of Pathology and Forensics Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianhong","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Tumor Stem Cell Research of Liaoning Province Dalian Medical University  Dalian China"},{"name":"Department of Pathology and Forensics Dalian Medical University  Dalian 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