Case Control Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2023; 29(22): 3482-3496
Published online Jun 14, 2023. doi: 10.3748/wjg.v29.i22.3482
Plasma exosomal hsa_circ_0079439 as a novel biomarker for early detection of gastric cancer
Xiao Li, Yan-Li Lin, Jia-Kang Shao, Xiao-Jie Wu, Xiang Li, He Yao, Fa-Liang Shi, Long-Song Li, Wen-Gang Zhang, Zheng-Yao Chang, Ning-Li Chai, You-Liang Wang, En-Qiang Linghu
Xiao Li, Long-Song Li, Wen-Gang Zhang, Ning-Li Chai, En-Qiang Linghu, Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
Xiao Li, Jia-Kang Shao, Long-Song Li, Wen-Gang Zhang, Zheng-Yao Chang, Medical School of Chinese PLA, Beijing 100853, China
Xiao Li, Yan-Li Lin, Xiao-Jie Wu, Xiang Li, He Yao, Fa-Liang Shi, You-Liang Wang, Beijing Institute of Biotechnology, Beijing 100071, China
Author contributions: Chai NL, Wang YL, and Linghu EQ designed the study; Li X, Shao JK, Li LS, Zhang WG, and Chang ZY collected the plasma samples; Li X, Lin YL, Wu XJ, Yao H, Shi FL, and Li X performed the dd-PCR test and data analysis; Li X, Lin YL, and Shao JK contributed equally to this work, and they should be considered as co-first authors; Chai NL, Wang YL, and Linghu EQ were co-corresponding authors; and all authors approved the final manuscript.
Supported by the National Key Research and Development Program, No. 2019YFA0903802, 2022YFC2503600, and 2016YFC1303601.
Institutional review board statement: This study was approved by the ethics committee of Chinese PLA General Hospital.
Informed consent statement: Informed consent was obtained from all participants in this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: En-Qiang Linghu, PhD, Chief Physician, Professor, Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. linghuenqiang@vip.sina.com
Received: April 16, 2023
Peer-review started: April 16, 2023
First decision: April 28, 2023
Revised: May 4, 2023
Accepted: May 11, 2023
Article in press: May 11, 2023
Published online: June 14, 2023
Processing time: 51 Days and 11.8 Hours
Abstract
BACKGROUND

Due to the poor prognosis of gastric cancer (GC), early detection methods are urgently needed. Plasma exosomal circular RNAs (circRNAs) have been suggested as novel biomarkers for GC.

AIM

To identify a novel biomarker for early detection of GC.

METHODS

Healthy donors (HDs) and GC patients diagnosed by pathology were recruited. Nine GC patients and three HDs were selected for exosomal whole-transcriptome RNA sequencing. The expression profiles of circRNAs were analyzed by bioinformatics methods and validated by droplet digital polymerase chain reaction. The expression levels and area under receiver operating characteristic curve values of plasma exosomal circRNAs and standard serum biomarkers were used to compare their diagnostic efficiency.

RESULTS

There were 303 participants, including 240 GC patients and 63 HDs, involved in the study. The expression levels of exosomal hsa_circ_0079439 were significantly higher in GC patients than in HDs (P < 0.0001). However, the levels of standard serum biomarkers were similar between the two groups. The area under the curve value of exosomal hsa_circ_0079439 was higher than those of standard biomarkers, including carcinoembryonic antigen, carbohydrate antigen (CA)19-9, CA72-4, alpha-fetoprotein, and CA125 (0.8595 vs 0.5862, 0.5660, 0.5360, 0.5082, and 0.5018, respectively). The expression levels of exosomal hsa_circ_0079439 were significantly decreased after treatment (P < 0.05). Moreover, the expression levels of exosomal hsa_circ_0079439 were obviously higher in early GC (EGC) patients than in HDs (P < 0.0001).

CONCLUSION

Our results suggest that plasma exosomal hsa_circ_0079439 is upregulated in GC patients. Moreover, the levels of exosomal hsa_circ_0079439 could distinguish EGC and advanced GC patients from HDs. Therefore, plasma exosomal hsa_circ_0079439 might be a potential biomarker for the diagnosis of GC during both the early and late stages.

Keywords: Gastric cancer; Exosomes; Circular RNA; Droplet digital polymerase chain reaction; Biomarker

Core Tip: Gastric cancer (GC) remains a prevalent disease worldwide. Due to its atypical clinical manifestations, GC is usually diagnosed at late stages in most patients and has a poor prognosis. Therefore, early detection of GC is of great importance. Based on the results of exosomal whole-transcriptome RNA sequencing, we performed bioinformatic analysis and droplet digital polymerase chain reaction (dd-PCR) tests. As validated by dd-PCR, exosomal hsa_circ_0079439 had a higher area under the curve value than standard biomarkers. Therefore, plasma exosomal hsa_circ_0079439 could serve as a novel biomarker for the early detection of GC.