Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2021; 27(42): 7311-7323
Published online Nov 14, 2021. doi: 10.3748/wjg.v27.i42.7311
Fusobacterium nucleatum colonization is associated with decreased survival of helicobacter pylori-positive gastric cancer patients
Yung-Yu Hsieh, Shui-Yi Tung, Hung-Yu Pan, Te-Sheng Chang, Kuo-Liang Wei, Wei-Ming Chen, Yi-Fang Deng, Chung-Kuang Lu, Yu-Hsuan Lai, Cheng-Shyong Wu, Chin Li
Yung-Yu Hsieh, Shui-Yi Tung, Te-Sheng Chang, Kuo-Liang Wei, Wei-Ming Chen, Yi-Fang Deng, Chung-Kuang Lu, Yu-Hsuan Lai, Cheng-Shyong Wu, Department of Gastroenterology and Hepatology, Chiayi Chang Gung Memorial Hospital, Chiayi 61301, Taiwan
Yung-Yu Hsieh, Shui-Yi Tung, Te-Sheng Chang, Kuo-Liang Wei, Wei-Ming Chen, Cheng-Shyong Wu, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Hung-Yu Pan, Department of Applied Mathematics, National Chiayi University, Chiayi 60035, Taiwan
Chin Li, Department of Biomedical Sciences, National Chung Cheng University, Chiayi 62130, Taiwan
Author contributions: Hsieh YY and Tung SY contributed equally to this work; Hsieh YY, Tung SY, Chang TS, Wei KL, Chen WM, and Wu CS recruited patients for the study and collected biopsies; Deng YF performed in vitro and sequencing experiments; Lai YH and Pan HY performed data and statistical analyses; Wu CS and Li C designed and supervised the study; Li C wrote the manuscript; All authors reviewed the manuscript.
Supported by Chiayi Chang Gung Memorial Hospital grants, including No. CORPG6G0021, No. CORPG6G0022 and No. CORPG6G0023 to Wu CS; No. CORPG6G0061, No. CORPG6G0062 and No. CORPG6G0063 to Tung SY; No. CORPG6G0071, No. CORPG6G0072 and No. CORPG6G0073 to Hsieh YY.
Institutional review board statement: All data acquisition and use of clinical specimens in this study were performed in accordance with the Declaration of Helsinki. Resected gastric cancer specimens were obtained from Tissue Bank, Department of Medical Research, Chang Gung Memorial Hospital at Chiayi. All the patients participating in this study were informed about the study and signed a written informed consent.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: Participants gave informed consent for data sharing.
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: Chin Li, PhD, Associate Professor, Department of Biomedical Sciences, National Chung Cheng University, No. 168, Section 1, University Road, Minhsiung, Chiayi 62130, Taiwan.
Received: April 11, 2021
Peer-review started: April 11, 2021
First decision: May 24, 2021
Revised: May 31, 2021
Accepted: September 14, 2021
Article in press: September 14, 2021
Published online: November 14, 2021
Research background

Our previous research identified Fusobacterium nucleatum (F. nucleatum) as an opportunistic pathogen frequently found in the gastric cancer-associated microbiota. F. nucleatum has been demonstrated to promote carcinogenesis and metastasis of colorectal cancer. However, the role of F. nucleatum in gastric cancer remains unclear.

Research motivation

It is our goal to determine the impact of F. nucleatum colonization to progression of gastric cancer.

Research objectives

The objective of current study is to identify the impact of F. nucleatum to the cellular function of gastric cancers and to the prognosis of gastric cancer patients.

Research methods

F. nucleatum-induced expression change of a patient-derived gastric cancer cell line was profiled by RNA sequencing and ontological analysis. The presence of F. nucleatum in patients' tumor tissue was determined by nested polymerase chain reaction. Statistical analysis of F. nucleatum colonization status was performed to determine the correlation with clinical characterization and patients' survival.

Research results

F. nucleatum induces a drastic but temporary interferon response and prolonged deregulation of actin and its regulators from gastric cancer cells. A survey of clinical specimens showed that approximately one-third of gastric cancer patients are positive for F. nucleatum. Survival analysis showed that the combined colonization of Helicobacter pylori (H. pylori) and F. nucleatum leads to poorer survival of late-stage patients.

Research conclusions

The actin filament dynamic change caused by F. nucleatum colonization likely promotes cell mobility and cancer metastasis. This observation is correlated with the finding that F. nucleatum colonization leads to poor survival of H. pylori-positive late-stage patients.

Research perspectives

F. nucleatum colonization leads to poorer survival of gastrectomy-received patients. Our findings indicate the importance of tumor-associated microbiota to the progression of gastric cancer.