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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2021; 13(4): 197-215
Published online Apr 15, 2021. doi: 10.4251/wjgo.v13.i4.197
Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside
Ming-Cheng Guan, Ming-Da Wang, Si-Yu Liu, Wei Ouyang, Lei Liang, Timothy M Pawlik, Qiu-Ran Xu, Dong-Sheng Huang, Feng Shen, Hong Zhu, Tian Yang
Ming-Cheng Guan, Wei Ouyang, Hong Zhu, Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Ming-Da Wang, Feng Shen, Tian Yang, Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, China
Si-Yu Liu, Department of Laboratory, Lishui Municipal Central Hospital, Lishui 323000, Zhejiang Province, China
Lei Liang, Qiu-Ran Xu, Dong-Sheng Huang, Tian Yang, Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310000, Zhejiang Province, China
Lei Liang, Qiu-Ran Xu, Dong-Sheng Huang, Tian Yang, Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
Timothy M Pawlik, Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH 43210, United States
Author contributions: Guan MC and Wang MD drafted the manuscript; Liu SY and Ouyang W prepared the figures and tables; Liang L and Xu QR provided input to the writing of this paper; Shen F and Pawlik TM provided critical comments; Huang DS, Zhu H, and Yang T designed the outline and coordinated the writing of the paper; Guan MC and Wang MD contributed equally to this work.
Supported by the National Natural Science Foundation of China (General Program), No. 81972726.
Conflict-of-interest statement: 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: Tian Yang, MD, Doctor, Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, No. 225 Changhai Road, Shanghai 200438, China. yangtian6666@hotmail.com
Received: December 21, 2020
Peer-review started: December 21, 2020
First decision: January 11, 2021
Revised: January 14, 2021
Accepted: March 11, 2021
Article in press: March 11, 2021
Published online: April 15, 2021
Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments. Despite being widely used, alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC. The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins, metabolites, circulating tumor deoxyribonucleic acid, and circulating non-coding ribonucleic acid. Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment, thus prolonging survival outcomes. Currently, multiple clinical trials involving locoregional, systemic therapies, and combinations of these modalities are changing therapeutic strategies for different stage HCC. Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future. This review summarizes the most recent advances in non-invasive early molecular detection, current therapy strategies, and potential immunotherapeutic innovations of HCC.

Keywords: Hepatocellular carcinoma, Early detection, Biomarker, Therapeutic strategies, Immunotherapeutic innovations

Core Tip: Long-term survival relies upon early diagnosis and timely treatment for patients with hepatocellular carcinoma (HCC). In this review, an update on the non-invasive early molecular detection and therapeutic strategies associated with HCC is discussed, focusing on omics-related biomarkers (e.g., proteins, metabolites, circulating tumor deoxyribonucleic acid, circulating non-coding ribonucleic acid), locoregional and systemic therapies for treating different stages of HCC, as well as potential immunotherapeutic innovations (e.g., adoptive cell transfer therapy).