The Korean Journal of Internal Medicine

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Original Article
Korean J Intern Med. 2025;40(4):571-583. Published online July 1, 2025.
DOI: https://doi.org/10.3904/kjim.2024.339
Distinct microbial signatures of liquid biopsy samples during gastric carcinogenesis and insights from extracellular vesicle analysis
Hee Sang You1,2, Jae Yong Park1, Hochan Seo1,2, Beom Jin Kim1, Jae Gyu Kim1 
1Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
2Laboratory of Gastrointestinal Mucosal Immunology, Chung-Ang University College of Medicine, Seoul, Korea
Corresponding author: Jae Gyu Kim ,Tel: +82-2-6299-3147, Fax: +82-2-749-9150, Email: jgkimd@cau.ac.kr
Received: September 26, 2024; Revised: December 19, 2024   Accepted: December 27, 2024.
Abstract
Background/Aims
The early detection of gastric cancer is crucial for improving patient outcomes. However, its pathogenesis is not fully understood. The microbiome and extracellular vesicles (EVs) might play a role in gastric carcinogenesis. We aimed to identify gastric-carcinogenesis-associated microbial signatures and evaluate whether these features vary across disease stages.

Methods
We enrolled 141 participants (132 patients with gastric cancer or dysplasia and 9 healthy controls). Microbial-derived EVs were isolated from gastric juice, saliva, serum, and urine. Next-generation sequencing of EV-derived bacterial DNA was performed.

Results
This sequencing revealed the alpha and beta diversities and microbial composition across different disease stages. The alpha diversity was significantly increased in the gastric juice and serum of disease groups. The beta diversity showed significant differences among patient groups. Distinct microbial signatures were observed across different disease stages in all four sample types. Specific bacterial species––Cutibacterium acnes, Streptococcus oralis, Pseudomonas antarctica, Ralstonia insidiosa, and Pseudomonas yamanorum––exhibited unique abundance patterns associated with disease progression, suggesting their potential as noninvasive biomarkers.

Conclusions
Changes in microbial diversity and distinct microbial signatures were observed during gastric carcinogenesis in both gastric juice and extragastric samples, indicating the potential of microbial-derived EVs from liquid biopsy samples as biomarkers for gastric cancer.

Keywords :Microbiome; Extracellular vesicles; Liquid biopsy; Stomach neoplasms; Biomarkers
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