Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

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Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study
Title:
Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study
Other Titles:
National Science Review
Publication Date:
29 October 2021
Citation:
Zhai, W., Lai, H., Kaya, N. A., Jianbin, C., Yang, H., Lu, B., … Chow, P. K.-H. (2021). Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study. National Science Review. doi:10.1093/nsr/nwab192
Abstract:
Abstract Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the Singapore National Medical Research Council - Translational and Clinical Research (TCR)
Grant Reference no. : TCR/015-NCC/2016

This research / project is supported by the National Research Foundation - NRF Fellowship
Grant Reference no. : NRF-NRFF2015-04

This research / project is supported by the Ministry of Health - Clinician Scientist - Individual Research Grant
Grant Reference no. : CIRG18may-0057l

This research / project is supported by the National Medical Research Council - Clinician Scientist Award - Senior Investigator (CSA-SI)
Grant Reference no. : NMRC/CSA-SI/0018/2017

This research / project is supported by the National Medical Research Council - Open Fund - Individual Research Grant (OFIRG)
Grant Reference no. : NMRC/OFIRG/0064/2017

i) National Key R&D program of China (grant 2018YFC1406902 and 2018YFC0910400) ii) National Science Foundation of China (grant no. 31970566) iii) Strategic Priority Research Program of the Chinese Academy of Sciences XDPB17 (XDPB17) iv) National Science Foundation of China (grant no. 32000407)
Description:
ISSN:
2053-714X
2095-5138