{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:08:40Z","timestamp":1789837720403,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20gm0910004"],"award-info":[{"award-number":["JP20gm0910004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21ak0101179"],"award-info":[{"award-number":["21ak0101179"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Owing to the lack of definite diagnostic modalities, it is challenging to distinguish malignant cases of cholangiocarcinoma (CCA), which often causes biliary tract obstruction, from benign ones. Here, we investigated a novel lipid biomarker of CCA in bile\u2010derived small extracellular vesicles (sEVs) and developed a simple detection method for clinical application.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bile samples from seven patients with malignant diseases (hilar CCA\u2009=\u20094, distal CCA\u2009=\u20093) and eight patients with benign diseases (gallstones\u2009=\u20096, primary sclerosing cholangitis\u2009=\u20091, autoimmune pancreatitis\u2009=\u20091) were collected through a nasal biliary drainage tube. sEVs were isolated via serial ultracentrifugation and characterized using nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting (with CD9, CD63, CD81, and TSG101). Comprehensive lipidomic analysis was performed using liquid chromatography\u2013tandem mass spectrometry. Using a measurement kit, we further confirmed whether lipid concentrations could be used as a potential CCA marker.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lipidomic analysis of bile sEVs in the two groups identified 209 significantly increased lipid species in the malignant group. When focusing on lipid class, phosphatidylcholine (PC) level was 4.98\u2010fold higher in the malignant group than in the benign group (P\u2009=\u20090.037). The receiver operating characteristic (ROC) curve showed a sensitivity of 71.4%, a specificity of 100%, and an area under the curve (AUC) of 0.857 (95% confidence interval [CI]:0.643\u20131.000). Using a PC assay kit, the ROC curve showed a cutoff value of 16.1\u2009\u03bcg\/mL, a sensitivity of 71.4%, a specificity of 100%, and an AUC of 0.839 (95% CI: 0.620\u20131.000).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PC level in sEVs from human bile is a potential diagnostic marker for CCA and can be assessed by a commercially available assay kit.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5973","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T10:58:44Z","timestamp":1682420324000},"page":"13007-13018","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Phosphatidylcholine in bile\u2010derived small extracellular vesicles as a novel biomarker of cholangiocarcinoma"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-3506","authenticated-orcid":false,"given":"Ryuta","family":"Muraki","sequence":"first","affiliation":[{"name":"Second Department of Surgery Hamamatsu University School of Medicine  Hamamatsu Japan"},{"name":"Department of Cellular and Molecular Anatomy Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshifumi","family":"Morita","sequence":"additional","affiliation":[{"name":"Second Department of Surgery Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ida","sequence":"additional","affiliation":[{"name":"Second Department of Surgery Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Kitajima","sequence":"additional","affiliation":[{"name":"Second Department of Surgery Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Furuhashi","sequence":"additional","affiliation":[{"name":"Second Department of Surgery Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1523-1103","authenticated-orcid":false,"given":"Makoto","family":"Takeda","sequence":"additional","affiliation":[{"name":"Second Department of Surgery Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotoshi","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Second Department of Surgery Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Second Department of Surgery Hamamatsu University School of Medicine  Hamamatsu Japan"},{"name":"Department of Perioperative Functioning Care &amp; 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