Proteomic Profiling of Extracellular Vesicles Reveals Potential Biomarkers for Helicobacter pylori Infection and Gastric Cancer

IF 4.3 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter Pub Date : 2025-03-03 DOI:10.1111/hel.70022

Phawinee Subsomwong, Krisana Asano, Junko Akada, Takashi Matsumoto, Akio Nakane, Yoshio Yamaoka

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Abstract

Background

Helicobacter pylori (H. pylori) has been identified as a type I carcinogen and contributes to a high rate of gastric cancer (GC), especially in Eastern Asia. Extracellular vesicles (EVs) have the potential to be used to detect various cancer types and diseases. However, the protein markers in EVs for the prognosis of H. pylori infection and GC are unknown. We aim to identify the proteins within EVs derived from a gastric epithelial cell line (AGS) infected with H. pylori by using LC-MS/MS.

Materials and Methods

EVs were isolated from AGS cells infected with high- and low-virulence H. pylori (strains TN2wt and Tx30a) by ultracentrifugation. Proteins within these EVs were identified and analyzed for potential marker candidates through bioinformatics. Proteins in H. pylori-derived EVs (HpEVs) from bacterial culture supernatant and HpEVs derived from H. pylori-infected AGS cells were elucidated.

Results

Differentially expressed proteins by proteomic analysis in AGSEVs-Tx30a vs. AGSEVs-noninfected (NI) and AGSEVs-TN2wt vs. AGSEVs-NI were 107 and 55 proteins, respectively. Bioinformatics of these proteomes revealed that essential proteins for H. pylori survival and pathogenicity including outer membrane proteins, metabolism-related, host cell infection-related, and virulence-related proteins were observed in HpEVs. Interestingly, EVs derived from AGS cells infected with H. pylori TN2wt significantly contained multiple proteins related to GC (ATP6V0A1, GAPDH, HINT1, LYZ, and RBX1).

Conclusion

This study provides a comprehensive protein profile of EVs from H. pylori-infected AGS cells and HpEVs, which could serve as liquid-based biomarkers in the future for screening H. pylori infection, especially GC-related.

Abstract Image

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细胞外囊泡的蛋白质组学分析揭示幽门螺杆菌感染和胃癌的潜在生物标志物

背景幽门螺杆菌（h.p ylori）已被确定为I型致癌物，是导致胃癌（GC）高发的原因，尤其是在东亚地区。细胞外囊泡（EVs）具有用于检测各种癌症类型和疾病的潜力。然而，EVs中与幽门螺杆菌感染和GC预后相关的蛋白标志物尚不清楚。我们的目的是利用LC-MS/MS技术鉴定幽门螺杆菌感染的胃上皮细胞系（AGS）衍生的ev中的蛋白质。材料与方法用超离心法从感染高、低毒力幽门螺杆菌（TN2wt和Tx30a）的AGS细胞中分离出ev。通过生物信息学对这些ev中的蛋白质进行鉴定和分析，以寻找潜在的候选标记物。研究了细菌培养上清中幽门螺杆菌源性ev （hpev）和幽门螺杆菌感染AGS细胞中hpev的蛋白表达。结果通过蛋白质组学分析，agsev - tx30a与agsev -non - infected （NI）、agsev - tn2wt与agsev -NI分别有107个和55个蛋白表达差异。这些蛋白质组学的生物信息学研究表明，hpev中存在幽门螺杆菌生存和致病性的必需蛋白，包括外膜蛋白、代谢相关蛋白、宿主细胞感染相关蛋白和毒力相关蛋白。有趣的是，来自幽门螺杆菌TN2wt感染的AGS细胞的ev显著含有多种与GC相关的蛋白（ATP6V0A1、GAPDH、HINT1、LYZ和RBX1）。结论本研究提供了幽门螺杆菌感染AGS细胞和hpev中EVs的全面蛋白图谱，可作为未来筛选幽门螺杆菌感染，特别是gc相关感染的液体生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Helicobacter 医学-微生物学

CiteScore

8.40

自引率

9.10%

发文量

审稿时长

2 months

期刊介绍： Helicobacter is edited by Professor David Y Graham. The editorial and peer review process is an independent process. Whenever there is a conflict of interest, the editor and editorial board will declare their interests and affiliations. Helicobacter recognises the critical role that has been established for Helicobacter pylori in peptic ulcer, gastric adenocarcinoma, and primary gastric lymphoma. As new helicobacter species are now regularly being discovered, Helicobacter covers the entire range of helicobacter research, increasing communication among the fields of gastroenterology; microbiology; vaccine development; laboratory animal science.