Biotransformation-based metabolomics profiling method for determining and quantitating cancer-related metabolites.

The discovery and identification of reliable disease biomarkers and relevant disrupted metabolic pathways is still a major challenge in metabolomics. Here, we proposed a biotransformation-based metabolomics profiling method to identify reliable disease biomarkers by simultaneous quantitation and qualification of cancer-related metabolites and their metabolic pathways via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The approach was based on selecting a subset of known cancer-related metabolites from our previous metabolomics work, cancer research literature and biological significance. The metabolic profiling of pathway-related metabolites was developed by predicted multiple reaction monitoring (MRM) of ion pairs based on their chemical structures and biotransformation. Then, a high-throughput quantitative method was established. Overall, this approach enables the sensitive and accurate detection of cancer-related metabolites and the identification of other relevant metabolites, which facilitates better data quality and in-depth investigation of dysregulated metabolic pathways. As a proof of concept, the approach was applied to a small-cell lung cancer (SCLC) study. The results showed that 43 metabolites were significantly changed, and arginine metabolism was apparently disturbed, which proved the proposed approach could be a powerful tool for discovering reliable disease biomarkers and aberrant metabolic pathways.