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Serum TFF levels were measured by ELISA. Organ-specific TFF3 expression, cytokine profiles, STAT3 activation, and epigenetic regulation were analyzed using RT-PCR, immunohistochemistry, multiplex assays, Western blotting, and ChIP\u2013qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum TFF1\u20133 levels were significantly elevated in gastric cancer\u2013bearing mice, with TFF3 showing robust diagnostic performance. In rats, serum TFF3 levels remained unchanged after total gastrectomy. TFF3 expression was selectively upregulated in the liver, accompanied by STAT3 activation. Gastric IL-6 expression was increased, suggesting portal-mediated signaling to the liver. ChIP\u2013qPCR demonstrated sustained enrichment of H3K27ac at the TFF3 locus following IL-6 stimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increased serum TFF3 in gastric cancer originates from the liver and is associated with IL-6\u2013STAT3 signaling. Persistent elevation after gastrectomy may be explained by epigenetic activation, supporting the biological basis of TFF3 as a surrogate marker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10120-026-01782-3","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:22:30Z","timestamp":1784535750000},"page":"1001-1014","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatic origin of increased serum TFF3 in gastric cancer bearing subjects"],"prefix":"10.1007","volume":"29","author":[{"given":"Komei","family":"Kuge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Mukohyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Yasukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ishibashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasukazu","family":"Ohmoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Takeshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihisa","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Seto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Goldenring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikazu","family":"Ushijima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-6205","authenticated-orcid":false,"given":"Sachiyo","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"issue":"3","key":"1782_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2022","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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Other authors have nothing to declare.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiments were approved by the Animal Care and Utilization Committee of the National Institute of Health Sciences, Japan, and by The University of Tokyo Animal Care and Use Committee (approval number: 17-P-005), and were conducted in accordance with institutional guidelines and relevant regulations.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}