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In this retrospective single\u2010center study, we evaluated the prognostic value of transforming growth factor\u2010beta 1 (TGF\u2010\u03b21) and its relationship with programmed death\u2010ligand 1 (PD\u2010L1) expression. A total of 92 patients with surgically resected TETs, including 79 thymomas and 13 thymic carcinomas, were included. Immunohistochemical analyses were performed to assess the expression of TGF\u2010\u03b21, PD\u2010L1, phosphorylated Smad2 (pSmad2), and pSmad3. Associations between TGF\u2010\u03b21 expression and clinicopathological features were analyzed, and mechanistic interactions were investigated using two thymic carcinoma cell lines exposed to exogenous TGF\u2010\u03b21. High TGF\u2010\u03b21 expression was observed in 28% of patients and was significantly associated with advanced Masaoka stage (III\/IV), shorter tumor doubling time (median 328 vs. 713\u2009days,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.042), and lower 5\u2010year freedom from recurrence (FFR) rates (58.1% vs. 95.1%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001, log\u2010rank test). Coexpression of high TGF\u2010\u03b21 and PD\u2010L1 was linked to the poorest prognosis (5\u2010year FFR: 46.1%) and was identified as an independent predictor of recurrence (adjusted hazard ratio: 7.15; 95% confidence interval: 1.20\u201342.8). Immunohistochemically, TGF\u2010\u03b21 expression positively correlated with PD\u2010L1 and pSmad2\/3 expression. In\u00a0vitro, TGF\u2010\u03b21 stimulation upregulated PD\u2010L1 expression in a dose\u2010dependent manner, accompanied by increased pSmad2\/3 activation. These findings indicate that high TGF\u2010\u03b21 expression demarcates a biologically aggressive TET phenotype and, together with PD\u2010L1, refines postoperative risk stratification, while its ability to drive PD\u2010L1 via Smad signaling could support the blockade of these pathways as a potential therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1111\/cas.70243","type":"journal-article","created":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T08:28:31Z","timestamp":1762590511000},"page":"181-192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transforming Growth Factor\u2010\u03b21 as a Biomarker of Malignant Behavior and\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    Expression in Thymic Epithelial Tumors"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8218-4185","authenticated-orcid":false,"given":"Chiaki","family":"Nakazono","sequence":"first","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2627-3587","authenticated-orcid":false,"given":"Satoru","family":"Okada","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"},{"name":"Institute\u2009of Pathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So","family":"Tando","sequence":"additional","affiliation":[{"name":"Department of Pathology and Applied Neurobiology Kyoto Prefectural University of Medicine Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunta","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6641-0078","authenticated-orcid":false,"given":"Tatsuo","family":"Furuya","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kameyama","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"K\u00fcffer","sequence":"additional","affiliation":[{"name":"Institute\u2009of Pathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute\u2009of Pathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Marx","sequence":"additional","affiliation":[{"name":"Institute\u2009of Pathology University Medical Center G\u00f6ttingen  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