Gas Biopsy for Pan-Cancer Mice Early Screening by Untargeted Mass Spectrometry Analysis of Metabolic VOCs

Early cancer detection is crucial for improving cure and survival rates. Pan-cancer detection technology enables simultaneous screening for multiple cancer types, representing a significant advancement in cancer diagnosis. Recent biomedical research suggests that cancer may function as a metabolic disorder, underscoring the importance of multiomics, particularly metabolomics. Volatile organic compounds (VOCs) in metabolomics provide noninvasive methods for early disease screening. However, a reliable strategy for VOC analysis in early pan-cancer detection is currently lacking. In this study, we established a N-Nitrosodiethylamine (DEN)-ethanol induction pan-cancer mouse model to longitudinally monitor metabolomic samples (urine, feces, and odor) for VOCs throughout the entire tumor growth process. We employed headspace solid-phase microextraction-gas chromatography–mass spectrometry (HS-SPME-GC-MS) technology for untargeted tracking and profiling of tumor growth. Through statistical analysis, we identified characteristic metabolites from different metabolomic samples and determined their corresponding early screening time points. These VOCs demonstrated excellent performance in distinguishing tumor development and assessing differences between tumor and healthy groups in validation analyses. This study emphasizes the potential of VOCs in noninvasive whole cancer screening and early diagnosis, providing a fundamental reference for VOCs based gas biopsy experiments in preclinical stages, and demonstrating the concept of early tumor detection.