Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2019; 25(13): 1580-1591
Published online Apr 7, 2019. doi: 10.3748/wjg.v25.i13.1580
Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer
Xiao-Liang Zhu, Long-Fei Ren, Hai-Ping Wang, Zhong-Tian Bai, Lei Zhang, Wen-Bo Meng, Ke-Xiang Zhu, Fang-Hui Ding, Long Miao, Jun Yan, Yan-Ping Wang, Yu-Qin Liu, Wen-Ce Zhou, Xun Li
Xiao-Liang Zhu, Long-Fei Ren, Lei Zhang, Fang-Hui Ding, Xun Li, The Fifth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Hai-Ping Wang, The Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Zhong-Tian Bai, Ke-Xiang Zhu, Long Miao, Jun Yan, Wen-Ce Zhou, The Second Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Wen-Bo Meng, The Department of Minimally invasive surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Yan-Ping Wang, The Pharmacy Department, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Yu-Qin Liu, Cancer Epidemiology Research Center, Gansu Cancer Hospital, Lanzhou 730050, Gansu Province, China
Author contributions: Zhu XL, Wang YP, Zhou WC and Li X contributed to conceptualization and design of the study, and Liu YQ suggested the study location. Zhu XL, Zhang L, Meng WB, Zhu KX, Ding FH and Miao L performed all gastroscopy and collected the blood and biopsy samples. Ren LF, Wang HP, Bai ZT and Yan J performed the majority of the experiments and analyzed the data. All authors drafted the article and made revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Supported by the Health Industry Research Project of Gansu Province, No. GSWSKY2017-26; the Gansu Province Science Foundation for Distinguished Young Scholars, No. 1606RJDA317; the Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, No. zdsyskfkt-201704; and the Foundation of The First Hospital of Lanzhou University, No. ldyyyn2015-16.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the First Hospital of Lanzhou University. Informed consent was obtained from all individual participants included in the study.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: Xun Li, MD, Chief Doctor, The Fifth Department of General Surgery, The First Hospital of Lanzhou University, No.1 DongGang West Road, Lanzhou 730000, Gansu Province, China. lxdr21@126.com
Telephone: +86-931-8356821 Fax: +86-931-8619797
Received: January 9, 2019
Peer-review started: January 9, 2019
First decision: February 13, 2019
Revised: March 1, 2019
Accepted: March 11, 2019
Article in press: March 12, 2019
Published online: April 7, 2019
Processing time: 85 Days and 11.3 Hours
ARTICLE HIGHLIGHTS
Research background

The early gastric cancer means the gastric mucosal lesion and the development of invasion cancer do not reach the submucosa, but their spread is limited to the mucous layer. Compared with advanced gastric cancer, it performs better in prognosis. Yet due to the lack of typical symptoms and biomarkers, the early gastric cancer is hard to be diagnosed and the golden standard is gastroscope. However, due to the patient's acceptance with certain risks and the difficulty in gastroscopic diagnosis, the detection rate of early gastric cancer in China is still low. Some existed research suggests that microRNA (miRNA) in the peripheral blood can be used as biomarkers in the diagnosis and prognosis of gastric cancer especially for advanced gastric cancer, but few shows whether miRNA can be used as the biomarker for predictive diagnosis of early gastric cancer.

Research motivation

MiRNA is relatively stable in the circulation system, and the detection technique is simple and easy to popularize. The several combinations of miRNAs can improve the accuracy of diagnosis which found in kinds of cancers. Through the predictive diagnosis model of the combination of several miRNAs, screening out high-risk or suspect patients and then being confirmed by gastroscopy combined with biopsy, will improve the accuracy and efficiency of gastroscopy, and promote the detection of early gastric cancer and early diagnosis of advanced gastric cancer, thereby improving the overall treatment effect and prognosis of gastric cancer.

Research objectives

The focus of the study is whether miRNA in peripheral blood can be used as sensitive and specific biomarkers for predictive diagnosis of early gastric cancer. First of all, it is to be studied that whether there is one or there are several miRNAs used to diagnose gastric cancer and non-cancer. Furthermore, it is to be known that whether such miRNAs can be used to suggest the occurrence of early gastric cancer. If there are indeed such miRNAs, it needs to be known that whether it can be applied in the screening of early gastric cancer and the sensitivity and specificity as well as influence factors. All these are possibly applied to clinical practice.

Research methods

First, in the discovery set, miRNA array was applied to detect the differential expressions of plasma miRNA in the early and advanced gastric cancer patients as well as the control group. Then through the bioinformatics, miRNAs possibly related to disease staging were screened out. In the validation set, in order to rule out the effects of Helicobacter pylori (H. pylori) infection, atrophic gastritis and other diseases on miRNA, the control group was divided into H. pylori infection with atrophic gastritis and H. pylori-negative superficial gastritis. Then RT-qPCR was used to verify target miRNAs selected in the last stage and miRNAs or combinations that may be used for predictive diagnosis of early gastric cancer are selected.

Research results

Fourteen target miRNAs were screened from the miRNA array by bioinformatics and they show differential expressions in early and advanced gastric cancer and control group. Subsequent reverse transcription quantitative real-time polymerase chain reaction verification suggested that five miRNAs combinations might be used for predictive diagnosis of early and advanced gastric cancer while not being affected by diseases such as H. pylori infection and atrophic gastritis.

Research conclusions

In this article, we found that miRNAs in early and advanced gastric cancer as well as control group show differential expressions. Through further confirmatory experiment, it is found that combinations of several miRNAs may suggest the occurrence of early and advanced gastric cancer. Gastroscopy combined with biopsy can be used to further confirm the diagnosis and then this combination of miRNAs may be regarded as the biomarker of predictive diagnosis of early gastric cancer.

Research perspectives

Currently, there is a lack of effective tumor biomarker in the diagnosis of gastric cancer, which is related to the heterogeneity of tumors. Although gastroscopy and biopsy are the golden standards for the diagnosis of gastric cancer, they are currently difficult to spread in China due to the large population. This study hopes to find high-risk patients with early gastric cancer in the population through simple and economical liquid biopsy of new miRNA biomarkers. Then gastroscope and pathological examination can be used to confirm the diagnosis and treatment of early gastric cancer, and early diagnosis and early treatment to advanced gastric cancer, so as to improve the overall prognosis and curative effect of gastric cancer. Certainly, the new combinations of these miRNAs biomarkers need to be further validated in a larger sample population.