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In this study, we investigated the role of CD109 in gallbladder adenocarcinoma (GBAC). CD109 expression in 77 resected GBAC samples was immunohistochemically evaluated. CD109 expression in tumor cells correlated with TNM stage, N factor, histological grade, lymphatic invasion, and perineural invasion and was associated with reduced disease\u2010free survival (DFS) and overall survival (OS). Stromal CD109 expression was detected in several cases, similar to that of \u03b1\u2010SMA and FAP, suggesting its presence in cancer\u2010associated fibroblasts. Stromal expression was also correlated with TNM stage, N factor, perineural invasion, and reduced DFS. Combined analysis of CD109 expression in tumor and stromal cells further stratified patients by prognosis. CD109 overexpression in GBAC cell lines induced the expression of the epithelial\u2010to\u2010mesenchymal transition (EMT) markers. Analyses using a public database revealed the association between CD109 and EMT\u2010related gene expression in biliary tract cancer cell lines. Moreover, CD109 depletion promoted enhanced transforming growth factor\u2010\u03b21\/Smad3 signaling and attenuated epidermal growth factor\/AKT signaling in GBAC cells in a cell type\u2010dependent manner. Collectively, these findings suggest that CD109 may serve as a prognostic biomarker of tumor progression and outcome in GBAC.<\/jats:p>","DOI":"10.1111\/pin.70085","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T18:30:11Z","timestamp":1768242611000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD109 Expression in Tumor and Stromal Cells Serves as a Prognostic Biomarker for Tumor Progression and Outcome in Gallbladder Adenocarcinoma"],"prefix":"10.1111","volume":"76","author":[{"given":"Taro","family":"Kogami","sequence":"first","affiliation":[{"name":"Department of Pathology Kitasato University School of Medicine Sagamihara Kanagawa Japan"},{"name":"Department of Gastroenterology Kitasato University School of Medicine Sagamihara Kanagawa 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