{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:59:15Z","timestamp":1791165555393,"version":"4.1.0"},"reference-count":26,"publisher":"The Korean Association for the Study of the Liver","issue":"3","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372985"],"award-info":[{"award-number":["82372985"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373418"],"award-info":[{"award-number":["82373418"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173260"],"award-info":[{"award-number":["82173260"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203561"],"award-info":[{"award-number":["82203561"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018558","name":"Shanghai Shuguang Program","doi-asserted-by":"crossref","award":["23SG09"],"award-info":[{"award-number":["23SG09"]}],"id":[{"id":"10.13039\/501100018558","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Medical Innovation Research Project","award":["22Y11907300"],"award-info":[{"award-number":["22Y11907300"]}]},{"name":"Shanghai Science and Technology Innovation Action Plan Project in Computational Biology","award":["24JS2840100"],"award-info":[{"award-number":["24JS2840100"]}]}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["Clin Mol Hepatol"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>Background\/Aims: Recurrence is a major factor limiting the long-term survival of patients with intrahepatic cholangiocarcinoma (ICC). The molecular characteristics and potential therapeutic targets in ICC remain largely undefined.Methods: Following our previous whole-exome sequencing study, we performed targeted sequencing, Sanger sequencing, and quantitative PCR to assess all coding exons and copy number variations of &lt;i&gt;LATS2&lt;\/i&gt; in 400 primary ICC samples. Kaplan\u2013Meier survival curves were used to assess the impact of &lt;i&gt;LATS2&lt;\/i&gt; mutation, copy number loss, and low expression levels on recurrence-free survival and overall survival in ICC patients. In addition, we investigated the functional role and underlying mechanisms of &lt;i&gt;LATS2&lt;\/i&gt; variation in ICC tumor progression and resistance to anti-PD-1 therapy.Results: Among a total of 400 ICC cases, the overall frequencies of &lt;i&gt;LATS2&lt;\/i&gt; somatic mutation and copy number loss were 3% (12\/400) and 34% (136\/400), respectively. Both types of variation were correlated with decreased LATS2 protein expression, increased tumor recurrence, and poor overall survival. Biofunctional investigations revealed a tumor-suppressor role of LATS2. Inactivation of &lt;i&gt;LATS2&lt;\/i&gt; suppressed the Hippo signaling pathway, leading to aberrant activation of YAP, which upregulated PD-L1 expression and CCL2 secretion, suppressed CD8&lt;sup&gt;+&lt;\/sup&gt; T cell infiltration, and enhanced recruitment of M2-like macrophages, thereby promoting immune evasion, tumor progression, and resistance to anti-PD-1 therapy.Conclusions: Our study reveals a pivotal clinical association and mechanistic role of &lt;i&gt;LATS2&lt;\/i&gt;-inactivating variation in ICC, which may serve as a useful biomarker for precision therapy.<\/jats:p>","DOI":"10.3350\/cmh.2025.0997","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:06:11Z","timestamp":1773821171000},"page":"1288-1304","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inactivating LATS2 variation drives tumor progression and resistance to anti-PD-1 therapy in intrahepatic cholangiocarcinoma"],"prefix":"10.3350","volume":"32","author":[{"given":"Ye","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Han","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu-Bin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Qiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 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