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The identification of predictive biomarkers that can enhance chemotherapy efficacy and inform immune modulation remains an urgent unmet need.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated the biological role and regulatory mechanisms of soluble AZGP1 in CCA using western blotting, ELISA, flow cytometry, and\n                      <jats:italic>in vitro\/in vivo<\/jats:italic>\n                      functional assays. A combination of pharmacological treatments and gene expression analyses was employed to explore pathway dynamics and immune responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that soluble AZGP1, which is typically downregulated in CCA, is significantly upregulated following 5-fluorouracil (5-FU) treatment. Mechanistically, 5-FU modulates the AKT\u2013Foxo1 signaling pathway, promoting nuclear translocation of Foxo1 and activation of AZGP1. Elevated soluble AZGP1 levels were shown to interact with PD-L1, enhancing apoptosis in cancer cells. Analyses of peripheral blood mononuclear cells (PBMCs) further confirmed the immune-modulating potential of AZGP1 in the tumor microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal that soluble AZGP1 acts as a predictive biomarker for 5-FU efficacy in cholangiocarcinoma and exerts pro-apoptotic and immunomodulatory functions via interaction with PD-L1. These insights may contribute to the development of more precise and effective therapeutic strategies in CCA treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-025-01362-8","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T10:41:52Z","timestamp":1758883312000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Secreted AZGP1 induced by 5-FU binds to PD-L1 and promotes apoptosis in cholangiocarcinoma"],"prefix":"10.1186","volume":"31","author":[{"given":"Ji-Eun","family":"You","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Yeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeseon","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-In","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yea Seong","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hoon","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"issue":"1","key":"1362_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-022-10404-x","volume":"23","author":"K Alwosaibai","year":"2023","unstructured":"Alwosaibai K, Aalmri S, Mashhour M, Ghandorah S, Alshangiti A, Azam F, et al. 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