{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:14:55Z","timestamp":1778854495593,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Gastroent Surgery"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Atezolizumab combined with bevacizumab is the standard first\u2010line therapy for unresectable hepatocellular carcinoma; however, predictive biomarkers of therapeutic response remain undefined. We aimed to identify molecular features associated with therapeutic efficacy to develop personalized treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Transcriptomic analyses were performed using public RNA\u2010sequencing datasets of patients with hepatocellular carcinoma receiving anti\u2010PD\u2010L1\u2010based therapy, comparing responders (complete response\/partial response) with non\u2010responders (stable disease\/progressive disease). Differentially expressed genes and enriched pathways were identified using integrated differential expression and pathway analysis. For validation, RNA\u2010sequencing was performed on institutional tumor samples (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096) underwent. Immunohistochemistry was performed on resected specimens (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099) to evaluate CD8+ tumor\u2010infiltrating lymphocytes and hepcidin protein expression encoded by the HAMP gene. Group comparisons for the pre\u2010specified immunohistochemistry endpoints were analyzed using exact Wilcoxon rank\u2010sum tests with multiplicity control (Holm adjustment).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis of public datasets revealed distinct expression profiles in responders, enriched in immune\u2010related and chemokine signaling pathways. Candidate genes, including HAMP, TAT, and HRG, were upregulated in responders. In institutional samples, HAMP expression was significantly higher in preoperatively treated tumors (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). Immunohistochemistry demonstrated greater CD8+ tumor\u2010infiltrating lymphocyte density (median 36.6 vs. 5.0 cells\/high\u2010power field; exact Wilcoxon\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032) and higher HAMP immunoreactive scores (median 4 vs. 0.5;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032) in responders than in non\u2010responders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Upregulation of HAMP and hepcidin protein expression, together with increased CD8+ T\u2010cell infiltration, was associated with a favorable response to atezolizumab\u2013bevacizumab in patients with hepatocellular carcinoma. HAMP may serve as a component of a composite biomarker predictive of therapeutic sensitivity, warranting validation in larger, multi\u2010institutional cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ags3.70158","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T02:09:56Z","timestamp":1767578996000},"page":"871-882","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of\n                    <scp>HAMP<\/scp>\n                    Expression and\n                    <scp>CD8<\/scp>\n                    + T\u2010Cell Infiltration With Atezolizumab\u2013Bevacizumab Response in Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6679-3677","authenticated-orcid":false,"given":"Shun","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine Oita University  Yufu Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Graduate School of Pharma\u2010Medical Sciences University of Toyama  Toyama Toyama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Oshima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine Oita University  Yufu Oita Japan"},{"name":"Graduate School of Pharma\u2010Medical Sciences University of Toyama  Toyama Toyama Japan"},{"name":"Faculty of Engineering University of Toyama  Toyama Toyama Japan"},{"name":"Research Center for Pre\u2010Disease Science University of Toyama  Toyama Toyama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine Oita University  Yufu Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Miyoshino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine Oita University  Yufu Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroomi","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine Oita University  Yufu Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Kawano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine Oita University  Yufu Oita 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