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

## TL;DR

The study explores how volatile compounds can reveal early signs of stomach cancer in mice, identifying enzymes that could serve as early biomarkers.

## Contribution

This work introduces induced volatolomics as a novel method for detecting enzymatic hallmarks of precancerous lesions.

## Key findings

- Upregulated α-mannosidase and β-galactosidase activities are linked to early Helicobacter infection.
- Increased β-Glucuronidase and β-N-acetyl-glucosaminidase activities signal progression to preneoplastic stages.
- VOC-based probes can monitor gastric cancer progression through tissue biopsies.

## 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.

•Induced volatolomics offers new opportunities by detecting volatile reporters released by activatable probes.•We identified upregulated glycosidases linked to infection or inflammatory processes in tissues infected by Helicobacter.•These enzymes may serve as early biomarkers for detecting gastric carcinogenesis.•This study highlights potential of VOC-based probes for monitoring of gastric cancer progression through tissue biopsies.•These findings could pave the way for more effective diagnostic strategies for early detection of carcinogenesis.

Induced volatolomics offers new opportunities by detecting volatile reporters released by activatable probes.

We identified upregulated glycosidases linked to infection or inflammatory processes in tissues infected by Helicobacter.

These enzymes may serve as early biomarkers for detecting gastric carcinogenesis.

This study highlights potential of VOC-based probes for monitoring of gastric cancer progression through tissue biopsies.

These findings could pave the way for more effective diagnostic strategies for early detection of carcinogenesis.