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

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.