{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:55:42Z","timestamp":1791446142865,"version":"4.3.3"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102020\u2010NR119695"],"award-info":[{"award-number":["RS\u20102020\u2010NR119695"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102022\u2010NR070833"],"award-info":[{"award-number":["RS\u20102022\u2010NR070833"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102024\u201000443043"],"award-info":[{"award-number":["RS\u20102024\u201000443043"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies and is characterized by a high degree of heterogeneity. However, HCC treatment remains difficult, highlighting the need to better define molecular subgroups of HCC and understand their potential relationships with therapeutic response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we established 20 patient\u2010derived organoids and 12 patient\u2010derived cell lines from 20 individuals diagnosed with HCC. These models were comprehensively characterized using whole\u2010exome sequencing, RNA sequencing, drug screening, and hepatitis B virus (HBV)\u2010targeting PCR with a focus on HBV\u2010related HCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Based on transcriptomic profiling, this study classified HCC into two molecular subtypes, aligning with previously reported classifications. Drug screening revealed that the greater enrichment of the PI3K\/AKT\/mTOR signalling pathway was associated with increased sensitivity to everolimus and lenvatinib. Integrated transcriptomic and drug\u2010response analyses further identified candidate genes associated with lenvatinib response. In addition, polymerase chain reaction (PCR) analysis targeting the HBV surface, core, and X genes demonstrated noticeable discrepancies relative to the clinically reported HBV infection status. Notably, HBV DNA detection was associated with activation of the calcium signalling pathway and oxaliplatin response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides a valuable resource for investigating the biology and pharmacological characteristics of HCC, particularly in the context of molecular subtypes and HBV\u2010associated mechanisms. Ultimately, these findings offer additional insights into HCC heterogeneity and drug response and may serve as a basis for further investigation of molecular determinants of therapeutic response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70853","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:37:27Z","timestamp":1791272247000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrative characterization of human hepatocellular carcinoma\u2010derived organoids and their HBV\u2010associated biology"],"prefix":"10.1002","volume":"16","author":[{"given":"Seo\u2010Hyeon","family":"Kim","sequence":"first","affiliation":[{"name":"Cancer Research Institute Seoul National University College of Medicine  Seoul South Korea"},{"name":"Department of Biomedical Sciences Seoul National University College of Medicine  Seoul South 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