A Comprehensive Metabolomics Analysis of Fecal Samples from Advanced Adenoma and Colorectal Cancer Patients

Abstract

Accurate diagnosis of colorectal cancer (CRC) still relies on invasive colonoscopy. Nonin-vasive methods are less sensitive in detecting the disease, particularly in the early stage. In the current work, a metabolomics analysis of fecal samples was carried out by ultra-high-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS). A total of 1380 metabolites were analyzed in a cohort of 120 fecal samples from patients with normal colonoscopy, advanced adenoma (AA) and CRC. Multivariate analysis revealed that metabolic profiles of CRC and AA patients were similar and could be clearly separated from control individuals. Among the 25 significant me-tabolites, sphingomyelins (SM), lactosylceramides (LacCer), secondary bile acids, polypeptides, formiminoglutamate, heme and cytidine-containing pyrimidines were found to be dysregulated in CRC patients. Supervised random forest (RF) and logistic regression algorithms were employed to build a CRC accurate predicted model consisting of the combination of hemoglobin (Hgb) and bil-irubin E,E, lactosyl-N-palmitoyl-sphingosine, glycocholenate sulfate and STLVT with an accuracy, sensitivity and specificity of 91.67% (95% Confidence Interval (CI) 0.7753–0.9825), 0.7 and 1, respectively.