{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T02:25:35Z","timestamp":1780971935527,"version":"3.54.1"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K16555"],"award-info":[{"award-number":["19K16555"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H03441"],"award-info":[{"award-number":["19H03441"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biliary tract cancer (BTC) is typically lethal due to the difficulty of early stage diagnosis. Thus, novel biomarkers of BTC precursors are necessary. Biliary intraepithelial neoplasia (BilIN) is a major precursor of BTC and is classified as low or high grade based on cell atypia. In normal gastric mucosa, gastric gland mucin\u2010specific <jats:italic>O<\/jats:italic>\u2010glycans are unique in having \u03b11,4\u2010linked <jats:italic>N<\/jats:italic>\u2010acetylglucosamine (\u03b1GlcNAc) attached to MUC6. Previously, we reported that \u03b1GlcNAc functions as a tumor suppressor of differentiated\u2010type gastric adenocarcinoma and that decreased \u03b1GlcNAc glycosylation on MUC6 in gastric, pancreatic, and uterine cervical neoplasms occurs in cancer as well as in their precursor lesions. However, \u03b1GlcNAc and MUC6 expression patterns in biliary tract neoplasms have remained unclear. Here, we analyzed MUC5AC, MUC6, and \u03b1GlcNAc expression status in 51 BTC cases and compared the expression of each with progression from low\u2010grade BilIN to invasive adenocarcinoma (IAC). The frequency of \u03b1GlcNAc\u2010positive and MUC6\u2010positive lesions decreased with tumor progression. When we compared each marker\u2019s expression level with tumor progression, we found that the MUC6 expression score in IAC was significantly lower than in low\u2010grade or high\u2010grade BilIN (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 or <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01, respectively). However, the \u03b1GlcNAc expression score was low irrespective of histological grade, and also lower than that of MUC6 across all histological grades (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 for low\u2010grade and high\u2010grade BilIN, and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01 for IAC). These results suggest that decreased expression of \u03b1GlcNAc relative to MUC6 marks the initiation of BTC progression.<\/jats:p>","DOI":"10.1111\/cas.14677","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T02:38:23Z","timestamp":1601951903000},"page":"4629-4635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Decreased alpha\u20101,4\u2010linked <i>N<\/i>\u2010acetylglucosamine glycosylation in biliary tract cancer progression from biliary intraepithelial neoplasia to invasive adenocarcinoma"],"prefix":"10.1111","volume":"111","author":[{"given":"Motohiro","family":"Okumura","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology Shinshu University School of Medicine Matsumoto Japan"},{"name":"Department of Surgery Shinshu University School of Medicine Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5361-8053","authenticated-orcid":false,"given":"Kazuhiro","family":"Yamanoi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology Shinshu University School of Medicine Matsumoto Japan"},{"name":"Department of Pathology Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Uehara","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Shinshu University Hospital Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6773-2802","authenticated-orcid":false,"given":"Jun","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology Shinshu University School of Medicine Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21262"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0446"},{"key":"e_1_2_7_4_1","first-page":"217","volume-title":"WHO Classification of Tumours of the Digestive System; World Health Organization of Tumours","author":"Nakanuma Y","year":"2010"},{"key":"e_1_2_7_5_1","first-page":"266","volume-title":"WHO Classification of Tumours of the Digestive System; World Health Organization of Tumours","author":"Albores\u2010Saavedra J","year":"2010"},{"key":"e_1_2_7_6_1","first-page":"265","volume-title":"WHO Classification of Tumours, Digestive System Tumours; World Health Organization of Tumours","author":"Kimstra DS","year":"2019"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3180409"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215540104900505"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13000"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.8991"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59087"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12305"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14165"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12728"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13317"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-018-2381-6"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49376-7"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2006.02414.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1267\/ahc.13027"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.09.025"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14677","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.14677","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:30:34Z","timestamp":1693297834000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.14677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,23]]},"references-count":19,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1111\/cas.14677"],"URL":"https:\/\/doi.org\/10.1111\/cas.14677","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,23]]},"assertion":[{"value":"2020-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}