Integrative characterization of human hepatocellular carcinoma‐derived organoids and their HBV‐associated biology
- 1Cancer Research Institute Seoul National University College of Medicine Seoul South Korea
- 2Department of Surgery Seoul National University College of Medicine Seoul South Korea
- 3Department of Surgery Seoul National University Hospital Seoul South Korea
Abstract
Background 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. Methods In this study, we established 20 patient‐derived organoids and 12 patient‐derived cell lines from 20 individuals diagnosed with HCC. These models were comprehensively characterized using whole‐exome sequencing, RNA sequencing, drug screening, and hepatitis B virus (HBV)‐targeting PCR with a focus on HBV‐related HCC. Results 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‐response 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. Conclusions This study provides a valuable resource for investigating the biology and pharmacological characteristics of HCC, particularly in the context of molecular subtypes and HBV‐associated 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.
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BibTeX
@article{kim2026integrative,
title = {{Integrative characterization of human hepatocellular carcinoma‐derived organoids and their HBV‐associated biology}},
author = {Seo‐Hyeon Kim and YoungRok Choi and Eun Woo Choi and Se Hui Kim and Seung Cheol Oh and Jae Yoon Kim and Su young Hong and Suk Kyun Hong and Kwang‐Woong Lee and Ja‐Lok Ku},
journal = {Clinical and Translational Medicine},
year = {2026},
month = oct,
doi = {10.1002/ctm2.70853},
url = {https://doi.org/10.1002/ctm2.70853},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrative characterization of human hepatocellular carcinoma‐derived organoids and their HBV‐associated biology
AU - Seo‐Hyeon Kim
AU - YoungRok Choi
AU - Eun Woo Choi
AU - Se Hui Kim
AU - Seung Cheol Oh
AU - Jae Yoon Kim
AU - Su young Hong
AU - Suk Kyun Hong
AU - Kwang‐Woong Lee
AU - Ja‐Lok Ku
PY - 2026
DA - 2026/10/26
JO - Clinical and Translational Medicine
DO - 10.1002/ctm2.70853
UR - https://doi.org/10.1002/ctm2.70853
AB - Background 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. Methods In this study, we established 20 patient‐derived organoids and 12 patient‐derived cell lines from 20 individuals diagnosed with HCC. These models were comprehensively characterized using whole‐exome sequencing, RNA sequencing, drug screening, and hepatitis B virus (HBV)‐targeting PCR with a focus on HBV‐related HCC. Results 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‐response 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. Conclusions This study provides a valuable resource for investigating the biology and pharmacological characteristics of HCC, particularly in the context of molecular subtypes and HBV‐associated 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.
SN - 2001-1326
ER -