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World J Gastrointest Oncol. May 15, 2021; 13(5): 351-365
Published online May 15, 2021. doi: 10.4251/wjgo.v13.i5.351
Biomarkers for hepatocellular carcinoma based on body fluids and feces
Ming-Cheng Guan, Wei Ouyang, Ming-Da Wang, Lei Liang, Na Li, Ting-Ting Fu, Feng Shen, Wan-Yee Lau, Qiu-Ran Xu, Dong-Sheng Huang, Hong Zhu, Tian Yang
Ming-Cheng Guan, Wei Ouyang, Na Li, Ting-Ting Fu, Hong Zhu, Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Ming-Da Wang, Feng Shen, Wan-Yee Lau, Tian Yang, Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai 200438, 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, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
Wan-Yee Lau, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
Author contributions: Guan MC and Ouyang W drafted the manuscript; Wang MD and Liang L prepared the figures and tables; Li N, Fu TT, and Xu QR provided important intellectual input in writing the paper; Shen F and Lau WY critically revised and finalized the draft; Huang DS, Zhu H, and Yang T designed the outline and coordinated the writing of the paper; Guan MC and Ouyang W contributed equally to this work.
Supported by National Natural Science Foundation of China, No. 81972726, No. 81871949 and No. 81572345.
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 17, 2021
Revised: January 18, 2021
Accepted: April 13, 2021
Article in press: April 13, 2021
Published online: May 15, 2021
Abstract

Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma (HCC). Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis, predicting responses to specific therapies, evaluating prognosis before or after therapy, as well as serving as novel therapeutic targets. Detection and analysis of proteins, metabolites, circulating nucleic acids, circulating tumor cells, and extracellular vesicles in body fluids (e.g., blood and urine) and gut microbiota (e.g., in feces) have excellent capabilities to improve different aspects of management of HCC. Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis, treatment, and monitoring responses of HCC to conventional therapies, most of which may improve diagnosis and management of HCC in the future. This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.

Keywords: Hepatocellular carcinoma, Biomarker, Blood, Urine, Feces, Gut microbiota

Core Tip: Hepatocellular carcinoma is the most frequently diagnosed malignancy of the liver, ranking as the fourth leading cause of cancer-related mortality worldwide. Recent developments of multiple novel biomarkers from body fluids and feces facilitate diagnosis and management of hepatocellular carcinoma. This review aimed to focus on these blood-, urine-, and feces-based biomarkers including proteins, metabolites, circulating nucleic acids, circulating tumor cells, extracellular vesicles, and gut microbiota on clinical application of these biomarkers.