Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis

doi:10.4251/wjgo.v12.i10.1195

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World Journal of Gastrointestinal Oncology

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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.

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
Processing time: 134 Days and 0.5 Hours

ARTICLE HIGHLIGHTS

Research background

Hepatocellular carcinoma (HCC) is common malignancy with high morbidity and mortality. The differential diagnosis of HCC from non-HCC is an urgent demand in clinical practice. However, there is a lack of effective non-invasive diagnosis methods for the differential diagnosis of HCC. Blood exosomal micro ribonucleic acids (miRNAs) have been reported as promising biomarkers in various types of cancer, when biopsy or resection is not the first choice.

Research motivation

To better distinguish between HCC patients and non-HCC patients, a convenient, non-invasive method with high accuracy is needed in clinical practice.

Research objectives

In this study, we aimed to characterize the blood exosomal miRNA profiling between HCC patients and non-HCC patients, and investigate the feasibility of blood exosomal miRNAs as potential biomarkers for differential diagnosis.

Research methods

Eighty-nine patients from Xiangya Hospital of Central South University were enrolled in this study between August 2017 and May 2018. The expression of blood exosomal miRNAs in these patients was assessed using miRNA sequencing.

Research results

We explored the characteristics of blood exosomal miRNAs in 89 patients with HCC and non-HCC patients, who were enrolled for cohort 1 (n = 44) and cohort 2 (n = 45). The analysis result of principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of non-HCC patients through miR-3168 and miR-223-3p. The blood exosomal miRNA profiles also revealed that some miRNAs are related to the stage of the tumor tissues. Based on the exosomal miRNA expression profiles of 89 patients, two pairs of miRNAs (miR-584-5p/miR-106-3p and miR-628-3p/miR-941) were established to identify HCC. The pairs of miRNAs showed a 94.1% sensitivity and 68.4% specificity to differentiate HCC patients from non-HCC patients. In addition, alcohol consumption habit was found to influence the specificity.

Research conclusions

Exosomal miRNAs miR-584-5p/miR-106-3p combined with miR-628-3p/miR-941 could distinguish HCC patients and non-HCC patients. However, tumor stage and alcohol consumption habits could affect the accuracy of the two pairs of blood exosomal miRNAs.

Research perspectives

This study suggested the potentiality of blood exosomal miRNAs as novel non-invasive diagnosis biomarkers to differentiate between HCC patients and non-HCC patients.