Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2020; 12(10): 1195-1208
Published online Oct 15, 2020. doi: 10.4251/wjgo.v12.i10.1195
Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis
Lang-Qing Sheng, Jia-Rong Li, Hao Qin, Ling Liu, Da-Dong Zhang, Qi Zhang, Meng-Li Huang, Xiao-Li Li, Xiao-Ya Xu, Yang-Nian Wei, Zi-Shuo Chen, Hui Luo, Ji-Yang Zhang, Cheng-Hui Zhou, Hao Chen, Ze-Guo Chen, Fu-Gen Li, Nian-Feng Li
Lang-Qing Sheng, Ling Liu, Qi Zhang, Xiao-Li Li, Yang-Nian Wei, Hui Luo, Cheng-Hui Zhou, Ze-Guo Chen, Nian-Feng Li, Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Jia-Rong Li, Department of Biliopancreatic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Hao Qin, Da-Dong Zhang, Xiao-Ya Xu, Zi-Shuo Chen, Ji-Yang Zhang, Hao Chen, Fu-Gen Li, Research and Development Institute of Precision Medicine, 3D Medicines Inc., Shanghai 201114, Hunan Province, China
Meng-Li Huang, The Medical Department, 3D Medicines Inc., Shanghai 201114, China
Author contributions: Li NF, Sheng LQ, Li JR, Qin H, and Zhang DD designed the experiments; Li NF, Sheng LQ, Li JR, Qin H, Liu L, Zhang DD, Zhang Q, Huang ML, Xu XY, Li XL, Chen ZS, Wei YN, Luo H, Zhou CH, Chen ZG, and Li FG performed the experiments and interpreted the data; Li NF, Qin H, Zhang DD, Zhang JY, and Chen H carried out data analysis; Li NF, Sheng LQ, Li JR, Qin H, and Zhang DD wrote and revised the manuscript.
Institutional review board statement: The study was approved by the ethics committee of Xiangya Hospital and informed consent was obtained from all patients or their relatives.
Conflict-of-interest statement: All authors with 3D Medicines affiliation are current or former employees. No potential conflicts of interest are disclosed by the other authors.
Data sharing statement: The data used to support the findings of this study are available from the corresponding author upon request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Nian-Feng Li, MD, Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital of Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan Province, China. 1535909540@qq.com
Received: June 2, 2020
Peer-review started: June 2, 2020
First decision: July 21, 2020
Revised: August 4, 2020
Accepted: August 31, 2020
Article in press: August 31, 2020
Published online: October 15, 2020
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a shortage of effective biomarkers for its diagnosis.

AIM

To explore blood exosomal micro ribonucleic acids (miRNAs) as potential biomarkers for HCC diagnosis.

METHODS
T
RESULTS

The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p. The miRNA profiles also revealed the tumor stages of HCC patients. High expression of miR-455-5p and miR-30c-5p, which significantly correlated with better overall survival in tumor tissues, could also be detected in blood exosomes. Two pairs of miRNAs (miR-584-5p/miR-106-3p and miR-628-3p/miR-941) showed a 94.1% sensitivity and 68.4% specificity to differentiate HCC patients from non-HCC patients. The specificity of the combination was substantially influenced by alcohol consumption habits.

CONCLUSION

This study suggested that blood exosomal miRNAs can be used as new non-invasive diagnostic tools for HCC. However, their accuracy could be affected by tumor stage and alcohol consumption habits.

Keywords: Blood exosomal micro ribonucleic acids, Biomarker, Differential diagnosis, Alcohol consumption habit, Hepatocellular carcinoma, Bioinformatics

Core Tip: To identify the potential biomarkers for hepatocellular carcinoma (HCC) diagnosis, we focused on exosomal micro ribonucleic acids (miRNAs) using miRNA sequencing. To our knowledge, this is the first study to explore the exosomal miRNAs for differential diagnosis of HCC using miRNA sequencing. This study provided a hint that blood exosomal miRNAs can be used as new non-invasive diagnostic tools for HCC in clinical implementation.