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Cellular and Molecular Biology

Presence of Fusobacterium nucleatum in relation to patient survival and an acidic environment in oesophagogastric junction and gastric cancers

British Journal of Cancer volume 131, pages 797–807 (2024)Cite this article

Subjects

Abstract

Background

Fusobacterium nucleatum inhabits the oral cavity and affects the progression of gastrointestinal cancer. Our prior findings link F. nucleatum to poor prognosis in oesophageal squamous cell carcinoma via NF-κB pathway. However, its role in oesophagogastric junction and gastric adenocarcinoma remains unexplored. We investigated whether F. nucleatum influences these cancers, highlighting its potential impact.

Methods

Two cohorts of EGJ and gastric adenocarcinoma patients (438 from Japan, 380 from the USA) were studied. F. nucleatum presence was confirmed by qPCR, FISH, and staining. Patient overall survival (OS) was assessed based on F. nucleatum positivity. EGJ and gastric adenocarcinoma cell lines were exposed to F. nucleatum to study molecular and phenotypic effects, validated in xenograft mouse model.

Results

In both cohorts, F. nucleatum-positive EGJ or gastric adenocarcinoma patients had notably shorter OS. F. nucleatum positivity decreased in more acidic tumour environments. Cancer cell lines with F. nucleatum showed enhanced proliferation and NF-κB activation. The xenograft model indicated increased tumour growth and NF-κB activation in F. nucleatum-treated cells. Interestingly, co-occurrence of F. nucleatum and Helicobacter pylori, a known risk factor, was rare.

Conclusions

F. nucleatum can induce the NF-κB pathway in EGJ and gastric adenocarcinomas, leading to tumour progression and poor prognosis.

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Fig. 1: Fusobacterium nucleatum (F. nucleatum) exacerbates the prognosis of oesophagogastric junction (EGJ) and gastric cancers.
Fig. 2: Number of Fusobacterium nucleatum (F. nucleatum)-positive cases or high F. nucleatum DNA cases and acidic environment in oesophageal cancer, oesophagogastric junction (EGJ) cancer, and gastric cancer.
Fig. 3: Fusobacterium nucleatum (F. nucleatum) promotes cell proliferation, migration, and invasion in oesophagogastric junction (EGJ) and gastric cancer cell lines.
Fig. 4: The NF-κB pathway and in vivo model.
Fig. 5: Association of Fusobacterium nucleatum (F. nucleatum) and Helicobacter pylori (H. pylori) in upper gastrointestinal cancer.

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Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank J. Iacona, Ph.D., from Edanz (https://jp.edanz.com/ac) for editing this manuscript.

Funding

This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (grant numbers 17H04273, 17K19702, and 17KK0195 to Y.B.).

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

    Yoshihiro Hara, Yoshifumi Baba, Eri Oda, Kazuto Harada, Kohei Yamashita, Tasuku Toihata, Keisuke Kosumi, Masaaki Iwatsuki, Yuji Miyamoto & Hideo Baba

  2. Division of Translational Research and Advanced Treatment Against Gastrointestinal Cancer, Kumamoto University, 1-1-1 Honjo, Chuoku, Kumamoto, 860-8556, Japan

    Yoshifumi Baba

  3. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Kohei Yamashita & Jaffer A. Ajani

  4. Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

    Hiroyasu Tsutsuki & Tomohiro Sawa

  5. Department of Pathology, UT M. D. Anderson Cancer Center, Houston, USA

    Qiong Gan & Rebecca E. Waters

  6. Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

    Yoshihiro Komohara

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  1. Yoshihiro Hara
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Contributions

YH conducted experiments and contributed to manuscript writing. YB provided guidance and supervision throughout the project. EO, KH, KY, TT, KK, MI, YM, and QG, REW were involved in data collection and analysis. HT and TS provided guidance on microbial experimental techniques. YK assisted in the confirmation of pathological specimens. JAA and HB supervised the project. All authors contributed to the conception, design, and interpretation of the study, and critically reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Yoshifumi Baba or Hideo Baba.

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The authors declare no competing interests.

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Informed consent was obtained from all the participants. This study was conducted in accordance with the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Kumamoto University (#1365).

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Hara, Y., Baba, Y., Oda, E. et al. Presence of Fusobacterium nucleatum in relation to patient survival and an acidic environment in oesophagogastric junction and gastric cancers. Br J Cancer 131, 797–807 (2024). https://doi.org/10.1038/s41416-024-02753-0

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