Exhaled volatolomics profiling facilitates personalized screening for gastric cancer

Gastric cancer (GC) is one of the most fatal cancers, characterized by non-specific early symptoms and difficulty in detection. However, there are no valid non-invasive screening tools available for GC. Here we establish a non-invasive method that employs exhaled volatolomics and ensemble learning to detect GC. We developed a comprehensive mass spectrometry-based procedure and determined of a wide range of volatolomics from 314 breath samples. The discovery, identification and verification research screened a biomarker panel to distinguish GC from controls. This panel has achieved 0.90 (0.87-0.94, 95%CI) accuracy, with an area under curve (AUC) of 0.92 (0.89-0.94, 95%CI) in discovery cohort and 0.88 (0.83-0.91, 95%CI) accuracy with an AUC of 0.91 (0.87-0.93, 95%CI) in replication cohort, which outperformed traditional serum markers. Single-cell sequencing and gene set enrichment analysis revealed that these exhaled markers originated from aldehyde oxidation and pyruvate metabolism. Our approach advances the design of exhaled analysis for GC detection and holds promise as a non-invasive method to the clinic.