Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare).

Abstract

Metabolomics is a valuable tool for biomarker screening of colorectal cancer (CRC). In this study, we profiled the urinary metabolomes of patients enrolled in a prospective patient cohort (ColoCare). We aimed to describe changes in the metabolome in the longer clinical follow-up and describe initial predictors as candidate markers with possibly prognostic significance. In total, 199 urine samples from CRC patients pre-surgery (n=97), 1-8 days post-surgery (n=12) and then after 6 and 12 months (n=52 and 38, respectively) were analyzed using both GC-MS and 1H-NMR. Both datasets were analyzed separately with built in uni- and multivariate analyses of Metaboanalyst 2.0. Furthermore, adjusted linear mixed effects regression models were constructed. Many concentrations of the metabolites derived from the gut microbiome were affected by CRC surgery, presumably indicating a tumor-induced shift in bacterial species. Associations of the microbial metabolites with disease stage indicate an important role of the gut microbiome in CRC.We were able to differentiate the metabolite profiles of CRC patients prior to surgery from those at any post-surgery timepoint using a multivariate model containing 20 marker metabolites (AUCROC=0.89; 95% CI:0.84-0.95). To the best of our knowledge, this is one of the first metabolomic studies to follow CRC patients in a prospective setting with repeated urine sampling over time. We were able to confirm markers initially identified in case-control studies and pin point metabolites which may serve as candidates for prognostic biomarkers of CRC.