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

As one of the most common tumors, gastric cancer (GC) has a high mortality rate, since current examination approaches cannot achieve early diagnosis. Fusobacterium nucleatum (Fn) primarily colonized in the oral cavity, has been reported to be involved in the development of gastrointestinal tumor. Until now, little is known about the relationship between salivary Fn and GC.


To determine whether salivary Fn could be a biomarker to diagnose GC and explore the influence of Fn on GC cells.


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 (GP) patients, and 20 normal controls (NC) from Qilu Hospital of Shandong University from January 2019 to December 2020. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of Fn as well as traditional serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4. Transwell assay and wound-healing assay were conducted to assess the influence of Fn infection on GC cells. The expression of epithelial-mesenchymal transition (EMT) markers was detected using western blot assay.


We found that the level of salivary Fn in GC patients was significantly increased compared with those in AG, NAG, and GP patients and NC (P < 0.001). ROC curve analysis showed a favorable capability of Fn (73.33% sensitivity; 82.14% specificity; area under the curve: 0.813) in GC diagnosis, which was superior to that of CEA, CA19-9, CA72-4, ferritin, and sialic acid. The Fn level in saliva of GC patients was increased as the TNM stage increased. GC patients with lymph node metastasis had higher Fn levels than those without metastasis. Both transwell and wound-healing assays indicated that Fn infection promoted the migration and invasion of GC cells. Western blot analysis showed that Fn infection decreased the expression of E-cadherin and increased the expressions of N-cadherin, vimentin, and snail.


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

Keywords: Gastric cancer, Fusobacterium nucleatum, Saliva, Prognosis, Metastasis, Epithelial-mesenchymal transition

Core Tip: Fusobacterium nucleatum (Fn), known as a periodontal pathogen, is frequently detected in tissues of gastrointestinal tumor. Here, we found that the level of salivary Fn was increased in gastric cancer (GC) patients, which could be used as a potential biomarker for GC diagnosis, and its diagnostic capability was superior to that of traditional serum tumor markers. We also showed that salivary Fn level was positively associated with the GC TNM stage and lymph node metastasis. Further, experiments in vitro revealed that Fn could promote the migration and invasion of GC cells by promoting the epithelial-mesenchymal transition process. Our findings suggest that salivary Fn is a potential biomarker in diagnosis of GC.