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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2020; 26(26): 3720-3736
Published online Jul 14, 2020. doi: 10.3748/wjg.v26.i26.3720
Intratumoral heterogeneity of hepatocellular carcinoma: From single-cell to population-based studies
Qi Zhang, Yu Lou, Xue-Li Bai, Ting-Bo Liang
Qi Zhang, Yu Lou, Xue-Li Bai, Ting-Bo Liang, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Qi Zhang, Yu Lou, Xue-Li Bai, Ting-Bo Liang, Key Laboratory of Pancreatic Disease of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
Qi Zhang, Xue-Li Bai, Ting-Bo Liang, Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
Qi Zhang, Xue-Li Bai, Ting-Bo Liang, Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang Province, China
Author contributions: Zhang Q and Lou Y contributed equally to this work; Zhang Q conceived the idea; Lou Y performed the search; Liang T and Bai X interpreted the clinical significance; Zhang Q and Lou Y drafted the manuscript; all authors made critical revision and approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81871320 and No. 81830089; and Zhejiang Provincial Natural Science Foundation of China, No. LR20H160002.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ting-Bo Liang, MD, PhD, FACS, Chief Doctor, Professor, Research Fellow, Surgeon, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Hangzhou 310003, Zhejiang Province, China. liangtingbo@zju.edu.cn
Received: February 27, 2020
Peer-review started: February 27, 2020
First decision: May 21, 2020
Revised: June 2, 2020
Accepted: June 18, 2020
Article in press: June 18, 2020
Published online: July 14, 2020
Abstract

Hepatocellular carcinoma (HCC) is characterized by high heterogeneity in both intratumoral and interpatient manners. While interpatient heterogeneity is related to personalized therapy, intratumoral heterogeneity (ITH) largely influences the efficacy of therapies in individuals. ITH contributes to tumor growth, metastasis, recurrence, and drug resistance and consequently limits the prognosis of patients with HCC. There is an urgent need to understand the causes, characteristics, and consequences of tumor heterogeneity in HCC for the purposes of guiding clinical practice and improving survival. Here, we summarize the studies and technologies that describe ITH in HCC to gain insight into the origin and evolutionary process of heterogeneity. In parallel, evidence is collected to delineate the dynamic relationship between ITH and the tumor ecosystem. We suggest that conducting comprehensive studies of ITH using single-cell approaches in temporal and spatial dimensions, combined with population-based clinical trials, will help to clarify the clinical implications of ITH, develop novel intervention strategies, and improve patient prognosis.

Keywords: Hepatocellular carcinoma, Tumor heterogeneity, Tumor microenvironment, Single-cell analysis, Local immunity

Core tip: We summarize the comprehensive studies of intratumoral heterogeneity (ITH) of hepatocellular carcinoma, including the different aspects, various dimensions, and clinical significance of ITH.