Metabolomics driven analysis of obesity-linked colorectal cancer patients via GC-MS and chemometrics: a pilot study

Abstract Colorectal cancer (CRC) is a major public health concern and one of the main causes of cancer-related deaths worldwide. Of different risk factors for developing CRC, obesity plays a vital key role in colorectal carcinogenesis due to the perturbation in the metabolic and lipid profiles of obese candidates. The aim of this study is to decipher the disturbed metabolites associated with CRC susceptibility in at-risk obese population along with their altered metabolic pathways via gas chromatography-mass spectrometry (GC-MS) metabolomics based approach. Multivariate chemometric methods including PCA and OPLS-DA in addition to different statistical tests were employed to detect the trends and determine the differential metabolites among the studied groups on a molecular level. The developed models unravelled the higher expression of novel metabolites in the sera of obese CRC patients belonging to fatty acids, organic acids and amino acids. Moreover, analysis of the associated metabolic pathways revealed the dysregulation of fatty acid metabolism, lactate and amino acid metabolism in obese CRC patients compared to their lean CRC and healthy control counterparts. This pilot study provides a useful insight regarding the mechanistic changes in metabolites related to CRC pathogenesis in obese patients in addition to the diagnostic performance of such metabolites as non-invasive screening option in obese CRC candidates.