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胃癌发生过程中液体活检样本的独特微生物特征及细胞外囊泡分析的见解

Distinct microbial signatures of liquid biopsy samples during gastric carcinogenesis and insights from extracellular vesicle analysis.

作者信息

You Hee Sang, Park Jae Yong, Seo Hochan, Kim Beom Jin, Kim Jae Gyu

机构信息

Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

Laboratory of Gastrointestinal Mucosal Immunology, Chung-Ang University College of Medicine, Seoul, Korea.

出版信息

Korean J Intern Med. 2025 Jul;40(4):571-583. doi: 10.3904/kjim.2024.339. Epub 2025 Jul 1.

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.

CONCLUSION

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.

摘要

背景/目的:早期发现胃癌对于改善患者预后至关重要。然而,其发病机制尚未完全明确。微生物群和细胞外囊泡(EVs)可能在胃癌发生过程中发挥作用。我们旨在识别与胃癌发生相关的微生物特征,并评估这些特征在不同疾病阶段是否有所不同。

方法

我们招募了141名参与者(132例胃癌或发育异常患者和9名健康对照)。从胃液、唾液、血清和尿液中分离微生物来源的细胞外囊泡。对细胞外囊泡衍生的细菌DNA进行二代测序。

结果

该测序揭示了不同疾病阶段的α和β多样性以及微生物组成。疾病组胃液和血清中的α多样性显著增加。β多样性在患者组之间存在显著差异。在所有四种样本类型中,不同疾病阶段均观察到独特的微生物特征。特定细菌种类——痤疮丙酸杆菌、口腔链球菌、南极假单胞菌、内氏罗尔斯通氏菌和山形假单胞菌——呈现出与疾病进展相关的独特丰度模式,表明它们作为非侵入性生物标志物的潜力。

结论

在胃癌发生过程中,胃液和胃外样本中均观察到微生物多样性的变化和独特的微生物特征,表明液体活检样本中微生物来源的细胞外囊泡作为胃癌生物标志物的潜力。

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