{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T18:46:54Z","timestamp":1787338014292,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to develop a deep learning (DL)-based multimodal framework that integrates magnetic resonance imaging (MRI), clinical, and laboratory data to predict programmed death ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) expression in Extrahepatic cholangiocarcinoma (eCCA) patients and assess the prognostic value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective cohort study involving 96 patients with eCCA was conducted across two institutions. A total of 16050 raw MRI images (11505 T1WI, 2371 T2WI, 2372 DWI) and 1570 tumor-containing images (990 T1WI, 289 T2WI, 291 DWI) were analyzed. Radiomic feature extraction was performed manually segmented tumor regions from MRI scans. The multimodal DL framework integrated DL features extracted from images and radiomic features as well as clinical-laboratory features through a repeated attention mechanism. Prognostic stratification was performed using Cox regression analysis to predict overall survival (OS) and evaluate the clinical utility of the model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The DL framework demonstrated moderate predictive performance for PD-L1 expression (AUC\u00a0=\u00a00.71) and good predictive capability for VEGF expression (AUC\u00a0=\u00a00.85) in the test cohort. The combination of DL-based imaging features and radiomic data outperformed single-modality approaches. Prognostic analysis revealed significant associations of model-predicted PD-L1 and VEGF expression with OS in eCCA patients. The Cox model-based nomogram demonstrated significant survival stratification (p = 0.006), with performance comparable to traditional immunohistochemistry-based methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings highlighted the potential of integrating DL and radiomics for non-invasive, preoperative biomarker profiling, offering a promising tool for personalized treatment strategies and improved clinical decision-making in eCCA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1658122","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T06:31:51Z","timestamp":1768285911000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Deep learning-based multimodal approach for non-invasive prediction and prognostic analysis of immune and angiogenic biomarkers in extrahepatic cholangiocarcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Jiong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruidan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinfei","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.03.008","article-title":"Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma","volume":"73","author":"Montal","year":"2020","journal-title":"J\u00a0Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00153-7","article-title":"Biliary tract cancer","volume":"397","author":"Valle","year":"2021","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: the next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.12.010","article-title":"Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry","volume":"76","author":"Izquierdo-Sanchez","year":"2022","journal-title":"J Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-023-01153-5","article-title":"Current standards, multidisciplinary approaches, and future directions in the management of extrahepatic cholangiocarcinoma","volume":"25","author":"Wheless","year":"2024","journal-title":"Curr Treat Options Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2310196","DOI":"10.1080\/07853890.2024.2310196","article-title":"Advances in targeted therapy of cholangiocarcinoma","volume":"56","author":"Li","year":"2024","journal-title":"Ann Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13045-020-01027-5","article-title":"Regulation of PD-L1 expression in the tumor microenvironment","volume":"14","author":"Yi","year":"2021","journal-title":"J Hematol Oncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"175586","DOI":"10.1016\/j.ejphar.2023.175586","article-title":"The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF","volume":"949","author":"Ghalehbandi","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"100251","DOI":"10.1016\/j.jhepr.2021.100251","article-title":"New insights on the role of vascular endothelial growth factor in biliary pathophysiology","volume":"3","author":"Mariotti","year":"2021","journal-title":"JHEP reports: Innovation hepatology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604129","article-title":"Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma","volume":"98","author":"Yoshikawa","year":"2008","journal-title":"Br J cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s10456-017-9552-y","article-title":"Anti-angiogenesis for cancer revisited:\u00a0Is there a role for combinations with immunotherapy","volume":"20","author":"Ramjiawan","year":"2017","journal-title":"Angiogenesis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00770-1","article-title":"Cholangiocarcinoma - novel biological insights and therapeutic strategies","volume":"20","author":"Ilyas","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0337-2","article-title":"The future of cancer immunotherapy: microenvironment-targeting combinations","volume":"30","author":"Murciano-Goroff","year":"2020","journal-title":"Cell Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","article-title":"Cholangiocarcinoma","volume":"7","author":"Brindley","year":"2021","journal-title":"Nat Rev Dis primers"},{"key":"B15","doi-asserted-by":"publisher","first-page":"103823","DOI":"10.1016\/j.critrevonc.2022.103823","article-title":"Prospective clinical research of radiomics and deep learning in oncology: A translational review","volume":"179","author":"Zhang","year":"2022","journal-title":"Crit\u00a0Rev oncology\/hematology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/mp.13678","article-title":"Machine and deep learning methods for radiomics","volume":"47","author":"Avanzo","year":"2020","journal-title":"Med physics"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djad046","article-title":"Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma","volume":"115","author":"Spencer","year":"2023","journal-title":"J Natl Cancer Inst"},{"key":"B18","doi-asserted-by":"publisher","first-page":"42","DOI":"10.20524\/aog.2017.0209","article-title":"New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin","volume":"31","author":"Bragazzi","year":"2018","journal-title":"Ann Gastroenterol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-1366","article-title":"Molecular mechanisms and future implications of VEGF\/VEGFR in cancer therapy","volume":"29","author":"Patel","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.857715","article-title":"A potential prognostic marker for recognizing VEGF-positive hepatocellular carcinoma based on magnetic resonance radiomics signature","volume":"12","author":"Fan","year":"2022","journal-title":"Front Oncol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"110141","DOI":"10.1016\/j.ejrad.2021.110141","article-title":"A radiomics model based on DCE-MRI and DWI may improve the prediction of estimating IDH1 mutation and angiogenesis in gliomas","volume":"147","author":"Wang","year":"2022","journal-title":"Eur J radiology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.894696","article-title":"A multiparametric method based on clinical and CT-based radiomics to predict the expression of p53 and VEGF in patients with spinal giant cell tumor of bone","volume":"12","author":"Wang","year":"2022","journal-title":"Front Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s00261-024-04427-0","article-title":"Radiomic\u00a0analysis based on magnetic resonance imaging for the prediction of VEGF expression in hepatocellular carcinoma patients","volume":"49","author":"Yang","year":"2024","journal-title":"Abdominal Radiol (New York)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s40364-023-00535-z","article-title":"Biomarkers and prognostic factors of PD-1\/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma","volume":"12","author":"Zhang","year":"2024","journal-title":"biomark Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3173","DOI":"10.3390\/cancers12113173","article-title":"Quantifying PD-L1 expression to monitor immune checkpoint therapy: opportunities and challenges","volume":"12","author":"Nimmagadda","year":"2020","journal-title":"Cancers"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32624","article-title":"Proteogenomic characterization of cholangiocarcinoma","volume":"77","author":"Deng","year":"2023","journal-title":"Hepatol (Baltimore Md)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13045-022-01253-z","article-title":"Immune cell atlas of cholangiocarcinomas reveals distinct tumor microenvironments and associated prognoses","volume":"15","author":"Xia","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"17588359211036544","DOI":"10.1177\/17588359211036544","article-title":"IMbrave 151: a randomized phase II trial of atezolizumab combined with bevacizumab and chemotherapy in patients with advanced biliary tract cancer","volume":"13","author":"Hack","year":"2021","journal-title":"Ther Adv Med Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1658122\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T06:31:53Z","timestamp":1768285913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1658122\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":28,"alternative-id":["10.3389\/fimmu.2025.1658122"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1658122","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]},"article-number":"1658122"}}