Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2022; 28(30): 4120-4132
Published online Aug 14, 2022. doi: 10.3748/wjg.v28.i30.4120
Salivary Fusobacterium nucleatum serves as a potential diagnostic biomarker for gastric cancer
Wen-Dan Chen, Xin Zhang, Meng-Jiao Zhang, Ya-Ping Zhang, Zi-Qi Shang, Yi-Wei Xin, Yi Zhang
Wen-Dan Chen, Xin Zhang, Meng-Jiao Zhang, Ya-Ping Zhang, Zi-Qi Shang, Yi-Wei Xin, Yi Zhang, Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Chen WD and Zhang X contributed equally to this work; Chen WD performed the research; Zhang X contributed to conception and revised the manuscript; Zhang YP collected the samples; Chen WD, Zhang MJ, Zhang YP, Shang ZQ, and Xin YW performed the experiments together; Zhang Y managed and coordinated the research, and provided the financial support; and all authors approved the final version of the article.
Supported by the National Natural Science Foundation of China, No. 81972005 and 82172339; the Natural Science Foundation of Shandong Province, No. ZR2020MH238; and Shandong Medical and Health Technology Development Project, No. 2018WS327.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Qilu Hospital of Shandong University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
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: Yi Zhang, PhD, Professor, Department of Clinical Laboratory, Qilu Hospital of Shandong University, No. 107 Wenhua Xi Road, Jinan 250012, Shandong Province, China.
Received: November 26, 2021
Peer-review started: November 26, 2021
First decision: January 8, 2022
Revised: January 21, 2022
Accepted: July 18, 2022
Article in press: July 18, 2022
Published online: August 14, 2022
Processing time: 256 Days and 18 Hours
Research background

Gastric cancer (GC) is a common malignant tumor in the digestive tract. Although the 5-year survival rate of GC is enhanced with the combination of chemotherapy and surgery, its mortality remains high due to the diagnosis at an advanced stage. It is essential to develop a new method to diagnose GC at an early stage.

Research motivation

Fusobacterium nucleatum (Fn) primarily colonized in the oral cavity, has been detected in tissues of GC in recent years. We wondered whether there is a correlation between salivary Fn and GC.

Research objectives

The research purpose was to find a new simple and effective biomarker to diagnose GC.

Research methods

The abundance of Fn in saliva was quantified by droplet digital polymerase chain reaction in 120 GC patients, 31 atrophic gastritis (AG) patients, 35 non-AG (NAG) patients, 26 gastric polyp patients, and 20 normal controls (NC). The diagnostic value of Fn was evaluated and compared with traditional serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, CA72-4, ferritin, and sialic acid. Transwell and wound-healing assays were conducted to assess the influence of Fn infection on GC cells. Western blot analysis was performed to detect the expression of epithelial-mesenchymal transition (EMT) markers.

Research results

Fn had favorable diagnostic value in classifying GC from NC and benign diseases, which was superior to those traditional serum tumor markers, such as CEA, CA19-9, CA72-4, ferritin, and sialic acid. Salivary Fn level was positively associated with the GC TNM stage and lymph node metastasis. Further, in vitro experiments revealed that Fn could promote the migration and invasion of GC cells. Western blot analysis indicated that Fn infection decreased the expression of epithelial marker such as E-cadherin, and increased the expression of mesenchymal markers such as N-cadherin, vimentin, and snail.

Research conclusions

Fn in saliva could be used as a promising biomarker to diagnose GC, and Fn infection could promote GC metastasis by accelerating the EMT process.

Research perspectives

Human saliva is a unique bio-fluid resource with huge clinical diagnostic and risk assessment capacity. Salivary Fn has promising value for diagnosing GC.