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World J Gastrointest Oncol. Sep 15, 2021; 13(9): 1144-1156
Published online Sep 15, 2021. doi: 10.4251/wjgo.v13.i9.1144
Characterization of metabolic landscape in hepatocellular carcinoma
Jing Wu, Ran Xue, Rong-Tao Jiang, Qing-Hua Meng
Jing Wu, Qing-Hua Meng, Department of Medical Oncology, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
Ran Xue, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100036, China
Rong-Tao Jiang, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
Author contributions: Meng QH and Wu J conceived and outlined the review; Wu J and Xue R performed the literature review and wrote the manuscript; Wu J and Jiang RT made critical revisions to the manuscript; all authors approved the final version.
Supported by The Municipal Natural Science Foundation of Beijing, China, No. 7192085; National Science and Technology Major Project of China, No. 2018ZX10302206-003-007 and No. 2017ZX10203202-001-005; The Capital Health Research and Development of Special, No. 2018-1-3011; and National Natural Science Foundation of China, No. 81470877.
Conflict-of-interest statement: The authors declare no conflicts of interest for this manuscript.
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: Qing-Hua Meng, MD, Chief Physician, Professor, Department of Medical Oncology, Beijing You-An Hospital, Capital Medical University, No. 8 Xi Tou Tiao, Youanmen Wai, Fengtai District, Beijing 100069, China. meng_qh0805@ccmu.edu.cn
Received: May 8, 2021
Peer-review started: May 8, 2021
First decision: June 16, 2021
Revised: June 29, 2021
Accepted: July 29, 2021
Article in press: July 29, 2021
Published online: September 15, 2021
Processing time: 125 Days and 11.8 Hours
Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, accounting for approximately 75%-85% of primary liver cancers. Metabolic alterations have been labeled as an emerging hallmark of tumors. Specially, the last decades have registered a significant improvement in our understanding of the role of metabolism in driving the carcinogenesis and progression of HCC. In this paper, we provide a review of recent studies that investigated the metabolic traits of HCC with a specific focus on three common metabolic alterations involving glycolysis, lipid metabolism, and glutamine addiction which have been gaining much attention in the field of HCC. Next, we describe some representative diagnostic markers or tools, and promising treatment agents that are proposed on the basis of the aforementioned metabolic alterations for HCC. Finally, we present some challenges and directions that may promisingly speed up the process of developing objective diagnostic markers and therapeutic options underlying HCC. Specifically, we recommend future investigations to carefully take into account the influence of heterogeneity, control for study-specific confounds, and invite the validation of existing biomarkers.

Keywords: Hepatocellular carcinoma; Metabolic reprogramming; Glycolysis; Lipid metabolism; Glutamine addiction; Diagnosis and treatment

Core Tip: Metabolic activities play a crucial role in promoting tumor transformation and progression. In the current review, we present a summary of recent advances investigating the metabolic traits of hepatocellular carcinoma (HCC) with a specific focus on three common metabolic alterations involving glycolysis, lipid metabolism, and glutamine addiction, and describe some representative diagnostic markers or tools, and promising treatment agents. Moreover, challenges related to the existence of great heterogeneity in HCC, the ignorance of study-related confounders, and a lack of validation of proposed markers are discussed.