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

利用诱导挥发组学揭示癌前病变的新酶学特征:小鼠胃癌前病变的概念验证

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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 Helicobacter felis infection in mice, mimicking the gastric carcinogenesis cascade induced by chronic Helicobacter pylori 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 Helicobacter 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.

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