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诱导挥发组学揭示癌前病变的新酶学特征:小鼠胃肿瘤前病变的概念验证

Induced volatolomics to uncover new enzymatic hallmarks of precancerous lesions: a proof of concept on gastric preneoplasia in mice.

作者信息

Eid Rony, Blochouse Estelle, Giese Alban, Papot Sébastien, Jay Philippe, Varon Christine, Poinot Pauline

机构信息

University of Poitiers, UMR CNRS 7285, Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Cedex 9, Poitiers, 86073, France.

University of Bordeaux, INSERM, UMR1312 BoRdeaux Institute of Oncology, F33000, Bordeaux, France.

出版信息

Biochem Biophys Rep. 2025 May 30;43:102062. doi: 10.1016/j.bbrep.2025.102062. eCollection 2025 Sep.

DOI:10.1016/j.bbrep.2025.102062
PMID:40519703
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12166735/
Abstract

Induced volatolomics is an emerging field of research that offers new opportunities in biology by detecting volatile reporters released by activatable probes, enabling the exploration of oncogenic processes. Building on its proven efficiency in exploring the evolution of implanted tumours, we hypothesized that induced volatolomics could extend its application to detect precancerous conditions. As a proof of concept, we performed a longitudinal study and investigated glycosidase activity during the early stages of gastric carcinogenesis development induced by infection in mice, mimicking the gastric carcinogenesis cascade induced by chronic infection in humans. We identified upregulated exoglycosidases linked to acute infections or inflammatory processes in tissues infected by Helicobacter. Specifically, α-mannosidase and β-galactosidase activities in stomach tissue were found to be strongly associated with the initial stages of infection. Additionally, the activities of β-Glucuronidase and β-N-acetyl-glucosaminidase increased during the progression to preneoplastic stages, potentially signalling the transition from infection to inflammation-driven carcinogenesis. These enzymes may serve as early biomarkers for detecting gastric carcinogenesis. Our study highlights the potential of VOC-based probes for real-time monitoring of gastric cancer progression through tissue biopsies. Therefore, this study demonstrates the potential of induced volatolomics for investigating biological processes and uncovering new therapeutic strategies.

摘要

诱导挥发物组学是一个新兴的研究领域,通过检测可激活探针释放的挥发性报告物,为生物学研究提供了新的机会,有助于探索致癌过程。基于其在研究植入肿瘤演变方面已被证实的效率,我们推测诱导挥发物组学可以扩展其应用范围,用于检测癌前病变。作为概念验证,我们进行了一项纵向研究,调查了小鼠感染诱导的胃癌发生发展早期阶段的糖苷酶活性,模拟了人类慢性感染诱导的胃癌发生级联反应。我们在感染幽门螺杆菌的组织中鉴定出与急性感染或炎症过程相关的外切糖苷酶上调。具体而言,发现胃组织中的α-甘露糖苷酶和β-半乳糖苷酶活性与感染的初始阶段密切相关。此外,在进展到癌前阶段的过程中,β-葡萄糖醛酸酶和β-N-乙酰氨基葡萄糖苷酶的活性增加,这可能标志着从感染到炎症驱动的致癌作用的转变。这些酶可能作为检测胃癌发生的早期生物标志物。我们的研究强调了基于挥发性有机化合物的探针通过组织活检实时监测胃癌进展的潜力。因此·这项研究证明了诱导挥发物组学在研究生物学过程和揭示新治疗策略方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c3/12166735/5007cf3ee8ef/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c3/12166735/aeb8fe87f81a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c3/12166735/ecc12a7a749f/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c3/12166735/5007cf3ee8ef/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c3/12166735/aeb8fe87f81a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c3/12166735/ecc12a7a749f/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c3/12166735/5007cf3ee8ef/mmcfigs2.jpg

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本文引用的文献

1
Glycosylation: mechanisms, biological functions and clinical implications.糖基化:机制、生物学功能和临床意义。
Signal Transduct Target Ther. 2024 Aug 5;9(1):194. doi: 10.1038/s41392-024-01886-1.
2
Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner.具核梭杆菌感染以依赖于氧的方式调节 HCT116 结直肠癌细胞的转录组和表观基因组。
Commun Biol. 2024 May 8;7(1):551. doi: 10.1038/s42003-024-06201-w.
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The role of -glycosylation in cancer.N-糖基化在癌症中的作用。 (注:原文中“-glycosylation”推测可能是“N-glycosylation”,不然“-糖基化”表意不明,这里按常见的“N-糖基化”进行了补充翻译)
Acta Pharm Sin B. 2024 Mar;14(3):1098-1110. doi: 10.1016/j.apsb.2023.10.014. Epub 2023 Oct 27.
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VOC-Based Probes, a New Set of Analytical Tools to Monitor Patient Health from Blood Sample. Proof of Concept on Tracking COVID-19 Infection.基于挥发性有机化合物的探针,一组新型分析工具,可从血液样本监测患者健康。用于追踪 COVID-19 感染的概念验证。
Anal Chem. 2023 Aug 8;95(31):11572-11577. doi: 10.1021/acs.analchem.3c01732. Epub 2023 Jul 5.
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Induced-volatolomics for the design of tumour activated therapy.用于肿瘤激活疗法设计的诱导挥发物组学
Chem Sci. 2023 Apr 11;14(18):4697-4703. doi: 10.1039/d2sc06797h. eCollection 2023 May 10.
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Induced volatolomics of pathologies.疾病的诱导挥发物组学
Nat Rev Chem. 2021 Mar;5(3):183-196. doi: 10.1038/s41570-020-00248-z. Epub 2021 Feb 2.
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Helicobacter pylori infection.幽门螺杆菌感染。
Nat Rev Dis Primers. 2023 Apr 20;9(1):19. doi: 10.1038/s41572-023-00431-8.
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Establishment of blood glycosidase activities and their excursions in sepsis.脓毒症中血糖苷酶活性的建立及其变化
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The current and future incidence and mortality of gastric cancer in 185 countries, 2020-40: A population-based modelling study.2020 - 2040年185个国家胃癌的当前及未来发病率和死亡率:一项基于人群的建模研究
EClinicalMedicine. 2022 Apr 21;47:101404. doi: 10.1016/j.eclinm.2022.101404. eCollection 2022 May.
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Targeting Glycosylation: A New Road for Cancer Drug Discovery.靶向糖基化:癌症药物发现的新途径。
Trends Cancer. 2020 Sep;6(9):757-766. doi: 10.1016/j.trecan.2020.04.002. Epub 2020 May 4.