{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:08:17Z","timestamp":1793678897279,"version":"4.5.1"},"reference-count":28,"publisher":"The Korean Association for the Study of the Liver","issue":"3","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20210968"],"award-info":[{"award-number":["BK20210968"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102150"],"award-info":[{"award-number":["82102150"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["CMH"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:p>Background\/Aims: Identifying patients with intrahepatic cholangiocarcinoma (ICC) likely to benefit from immunochemotherapy, the new front-line treatment, remains challenging. We aimed to unveil a novel radiotranscriptomic signature that can facilitate treatment response prediction by multi-omics integration and multiscale modelling.Methods: We analyzed bulk, single-cell and spatial transcriptomic data comprising 457 ICC patients to identify an immune-related score (IRS), followed by decoding its spatial immune context. We mapped radiomics profiles onto spatial-specific IRS using machine learning to define a novel radiotranscriptomic signature, followed by multi-scale and multi-cohort validation covering 331 ICC patients. The signature was further explored for the potential therapeutic target from in vitro to in vivo.Results: We revealed a novel 3-gene (PLAUR, CD40LG, and FGFR4) IRS whose down-regulation correlated with better survival and improved sensitivity to immunochemotherapy. We highlighted functional IRS-immune interactions within tumor epithelium, rather than stromal compartment, irrespective of geospatial locations. Machine learning pipeline identified the optimal 3-feature radiotranscriptomic signature that was well-validated by immunohistochemical assays in molecular cohort, exhibited favorable external prognostic validity with C-index over 0.64 in resection cohort, and predicted treatment response with an area under the curve of up to 0.84 in immunochemotherapy cohort. We also showed that anti-uPAR\/PLAUR alone or in combination with anti-programmed cell death protein 1 therapy remarkably curbed tumor growth, using in vitro ICC cell lines and in vivo humanized ICC patient-derived xenograft mouse models.Conclusions: This proof-of-concept study sheds light on the spatially-resolved radiotranscriptomic signature to improve patient selection for emerging immunochemotherapy and high-order immunotherapy combinations in ICC.<\/jats:p>","DOI":"10.3350\/cmh.2024.0895","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T02:37:28Z","timestamp":1739155048000},"page":"935-959","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Radiogenomics of intrahepatic cholangiocarcinoma predicts immunochemotherapy response and identifies therapeutic 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