{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:51:08Z","timestamp":1791179468692,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2026\u2010MS\u2010223"],"award-info":[{"award-number":["2026\u2010MS\u2010223"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Deficiency in SWItch\/Sucrose Non\u2010FermenTable (SWI\/SNF) related barrier\u2010to\u2010autointegration factor (BAF) chromatin remodeling complex subunit ATPase 4 (SMARCA4) drives aggressive behavior across various undifferentiated malignancies. However, its clinicopathological features, prognostic analysis, and molecular significance in undifferentiated digestive system malignancies, clinically rare and poorly characterized entities, remain incompletely elucidated. This study investigated the clinicopathological characteristics and prognostic significance of a retrospective cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200943). Immunohistochemistry (IHC) identified SMARCA4 deficiency in 30.2% of undifferentiated malignant tumors of the digestive system. Clinically, SMARCA4 deficiency constituted a significant poor\u2010prognosis predictor, correlating with poorer overall survival [OS; hazard ratio (HR)\u2009=\u20093.054, 95% confidence interval (CI) 1.277\u20137.306, log\u2010rank\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006] and disease\u2010free survival (DFS; HR\u2009=\u20092.717, 95% CI 1.129\u20136.539, log\u2010rank\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.015), independent of assessed lineage markers or microsatellite status. Integrated analysis of The Cancer Genome Atlas (TCGA) data of digestive system malignancies revealed that\n                    <jats:italic>SMARCA4<\/jats:italic>\n                    \u2010mutated tumors exhibited elevated tumor mutational burden (TMB) and distinct co\u2010mutation patterns. Notably,\n                    <jats:italic>SMARCA4<\/jats:italic>\n                    mutations significantly co\u2010occurred with multiple potentially actionable therapeutic targets, including receptor tyrosine kinases (\n                    <jats:italic>ERBB2<\/jats:italic>\n                    ,\n                    <jats:italic>ERBB3<\/jats:italic>\n                    ,\n                    <jats:italic>MET<\/jats:italic>\n                    , and\n                    <jats:italic>RET<\/jats:italic>\n                    ), DNA damage response genes (\n                    <jats:italic>BRCA2<\/jats:italic>\n                    ), and mismatch repair genes (\n                    <jats:italic>MLH1<\/jats:italic>\n                    ,\n                    <jats:italic>MSH2<\/jats:italic>\n                    ,\n                    <jats:italic>MSH6<\/jats:italic>\n                    ). Collectively, our findings identified SMARCA4 deficiency as a predictor of poor prognoses in digestive system malignancies, suggesting a distinct genomic context that may inform therapeutic stratification, including targeted and immunotherapeutic approaches, by focusing on these high\u2010frequency co\u2010mutated targets. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70107","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:22:36Z","timestamp":1787214156000},"page":"368-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>SMARCA4<\/scp>\n                    \u2010deficient undifferentiated malignancies in the digestive system: clinicopathological features and prognostic significance with genomic insights from the\n                    <scp>TCGA<\/scp>\n                    cohort"],"prefix":"10.1002","volume":"270","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3951-483X","authenticated-orcid":false,"given":"Yun\u2010Ran","family":"Guo","sequence":"first","affiliation":[{"name":"Central Laboratory The Fourth Affiliated Hospital of China Medical University  Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology Shengjing Hospital of China Medical University  Shenyang PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5964-0289","authenticated-orcid":false,"given":"Xiao","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute  Shenyang PR 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