Systematic Reviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2022; 14(1): 334-347
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.334
Exosomes as potential diagnosis and treatment for liver cancer
Xiao-Cui Wei, Li-Juan Liu, Fan Zhu
Xiao-Cui Wei, Li-Juan Liu, Fan Zhu, State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Pathogenic Biology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
Author contributions: Wei XC and Liu LJ equally contributed to this manuscript; Wei XC designed the research, drafted and revised the paper; Liu LJ analyzed the data, drafted and revised the paper; Zhu F was responsible for the design, edit, and revision of the article and supervised the manuscript; all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81971943 and No. 81772196; and the Medical Science Advancement Program (Clinical Medicine) of Wuhan University, No. TFLC 2018003.
Conflict-of-interest statement: All authors do not have any conflicts of interest relevant to this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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:
Corresponding author: Fan Zhu, PhD, Professor, State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Pathogenic Biology, School of Medicine, Wuhan University, No. 185 Donghu Road, Wuhan 430071, Hubei Province, China.
Received: March 22, 2021
Peer-review started: March 22, 2021
First decision: June 14, 2021
Revised: July 3, 2021
Accepted: September 8, 2021
Article in press: September 8, 2021
Published online: January 15, 2022

Liver cancer is the fourth most significant cause of cancer-related death. Lack of early diagnosis strategy and a scarcity of efficient therapy constitute the main reasons for its lethality. Exosomes, which contain various bioactive molecules, are characterized by high biocompatibility, low immunogenicity, and high transport efficiency. As a result, exosomes have become a research hotspot and present significant potential for cancer diagnosis biomarkers, biotherapeutics, therapy targets, drug carriers and therapeutic agents.


To explore the potential of exosomes in the diagnosis and treatment of liver cancer.


We conducted a systematic literature search via PubMed and Web of Science. The following keywords were used: "exosomal biomarkers", "exosomal therapy", "exosomal therapy", and "liver cancer" or "HCC". The duplicate data were deleted by EndNote software. Literature search focused on full-texts and references of each article were carefully checked. One author (Xiao-Cui Wei) screened the literature that met the following inclusion criteria: (1) Detection of exosomes or their contents in clinical samples (body fluid or tissue); or (2) Exosomes served as drug carriers or therapeutic factors. Two authors (Xiao-Cui Wei and Li-Juan Liu) independently reviewed all retained literature and analyzed the information.


A total of 1295 studies were identified using the systematic literature search. Of these, 835 duplicate studies were removed. A further 402 irrelevant studies were excluded due to being irrelevant, including other diseases, review articles, the literature containing neither clinical samples nor animal experiments, exosome-independent studies, methods for detecting exosomes, or articles in Chinese. Finally, 58 published papers were retained and analyzed in the study. It showed a list of potential exosomal biomarkers that were upregulated in the blood samples of patients with liver cancer. Those downregulated in exosomes might serve as possible biotherapeutics. Some exosomes derived from cells in vitro were used for cytology or animal experiments to explore the mechanism of these exosome contents in disease. These contents might serve as potential targets for liver cancer. Additionally, we also discussed that exosomes serve as drug carriers or therapeutic factors.


Exosomes might serve as potential biomarkers or therapeutic biotargets in liver cancer and have the potential to act as drug carriers and self-treatment factors for liver cancer patients.

Keywords: Exosomes, Liver cancer, Biomarker, Treatment, Drug delivery system

Core tip: We used a literature search to identify potential exosome diagnostic markers and novel therapeutic strategies for liver cancer. The latest literature was published in June 2021. Results were presented in tabular form, including 40 potential liver cancer biomarkers, 13 potential biotherapeutics, and 10 potential therapeutic targets for hepatocellular carcinoma. In addition, we also listed papers about exosomes as drug carriers and therapeutic factors.