Breathomics profiling facilitates personalized screening for colorectal cancer

Colorectal cancer (CRC) is the leading cause of cancer-related mortality, and early detection is key to improving survival. However, there are no reliable noninvasive tests currently available for CRC diagnosis. Here, through a combination of transcriptomics, breath profiling, and clinical analysis on carcinoma tissues and exhaled metabolites, significant dysregulation of short-chain fatty acid and aldehyde metabolism was identified during colorectal tumorigenesis. This metabolic perturbation was characterized by significant depletion of specific exhaled volatile organic compounds (VOCs), particularly propionic acid and butyric acid, along with concurrent elevation of alkanals including propanal and hexanal. Utilizing these VOC features, a comprehensive MS-based targeted assay using selected ion monitoring was developed, demonstrating a detection limit below 0.25 ng/L and accuracy ranging from 88.2 % to 105.2 %. The diagnostic model based on exhaled VOCs demonstrated superior performance with an AUC of 0.89 (95 % CI: 0.76-0.91), accuracy of 0.78, specificity of 0.77 and sensitivity of 0.86, outperforming serum markers (0.69, 0.69, 0.45, 0.66). This breath testing shows promise for early detection of CRC or large-scale screening of high-risk populations.