Chen, Jianbin and Kaya, Neslihan Arife and Zhang, Ying and Kendarsari, Raden Indah and Sekar, Karthik and Chong, Shay Lee and Seshachalam, Veerabrahma Pratap and Ling, Wen Huan and Phua, Cheryl Zi Jin and Lai, Hannah and Yang, Hechuan and Lu, Bingxin and Lim, Jia Qi and Ma, Siming and Chew, Sin Chi and Chua, Khi Pin and Alvarez, Jacob Josiah Santiago and Wu, Lingyan and Ooi, London and Chung, Alexander Yaw-Fui and Cheow, Peng Chung and Kam, Juinn Huar and Kow, Alfred Wei-Chieh and Ganpathi, Iyer Shridhar and Bunchaliew, Chairat and Thammasiri, Jidapa and Koh, Peng Soon and Ong, Diana Bee Lan and Lim, Jasmine and de Villa, Vanessa H. and Cruz, Rouchelle D. Dela and Loh, Tracy Jiezhen and Wan, Wei Keat and Leow, Wei Qiang and Yang, Yi and Liu, Jin and Skanderup, Anders Jacobsen and Pang, Yin Huei and Soon, Gwyneth Shook Ting and Madhavan, Krishnakumar and Lim, Tony Kiat-Hon and Bonney, Glenn and Goh, Brian K. P. and Chew, Valerie and Dan, Yock Young and Toh, Han Chong and Foo, Roger Sik-Yin and Tam, Wai Leong and Zhai, Weiwei and Chow, Pierce Kah-Hoe (2024) A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and `bad apple' effect on clinical trajectory. Journal of Hepatology, 81 (4). ISSN 0168-8278, DOI https://doi.org/10.1016/j.jhep.2024.05.017.
Full text not available from this repository.Abstract
Background & Aims: Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. Methods: Through the Asia-Pacific Hepatocellular Carcinoma trials group (NCT03267641), we recruited one of the largest prospective cohorts of patients with HCC, with over 600 whole genome and transcriptome samples from 123 treatment-na & iuml;ve patients. Results: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the `bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. Conclusions: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provides a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Education - Singapore, Agency for Science, Technology and Research, Singapore, National Natural Science Foundation of China [Grat no. 32293192/32293190, 31970566, 32000407, 92259303], National Research Foundation Singapore [Grant no. NRF-NRFF2015-04, NRF-NRFI08-2022, CRP23-2019-0072], National Medical Research Council [Grant no. NMRC/TCR/015-NCC/2016, NMRC/OFIRG/0064/2017, NMRC/CSA-SI/0018/2017, CIRG18may-0057, MOH-001067, NMRC/CIRG/1454/2016, TCR/015-NCC/2016], Chinese Academy of Sciences [Grant no. XDPB17] |
| Uncontrolled Keywords: | Hepatocellular carcinoma; Intra-tumoral heterogeneity; Multi-region tumor sampling; Tumor evolution; HCC clinical trajectory |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine > Surgery Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 22 Oct 2025 03:19 |
| Last Modified: | 22 Oct 2025 03:19 |
| URI: | http://eprints.um.edu.my/id/eprint/46475 |
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