Untargeted Metabolomics Reveals Major Differences in the Plasma Metabolome between Colorectal Cancer and Colorectal Adenomas

Sporadic colorectal cancer is characterized by a multistep progression from normal epithelium to precancerous low-risk and high-risk adenomas to invasive cancer. Yet, the underlying molecular mechanisms of colorectal carcinogenesis are not completely understood. Within the Metabolomic profiles throughout the continuum of colorectal cancer (MetaboCCC) consortium we analyzed data generated by untargeted, mass spectrometry-based metabolomics using plasma from 88 colorectal cancer patients, 200 patients with high-risk adenomas and 200 patients with low-risk adenomas recruited within the Colorectal Cancer Study of Austria (CORSA). Univariate logistic regression models comparing colorectal cancer to adenomas resulted in 442 statistically significant molecular features. Metabolites discriminating colorectal cancer patients from those with adenomas in our dataset included acylcarnitines, caffeine, amino acids, glycerophospholipids, fatty acids, bilirubin, bile acids and bacterial metabolites of tryptophan. The data obtained discovers metabolite profiles reflecting metabolic differences between colorectal cancer and colorectal adenomas and delineates a potentially underlying biological interpretation.

Automated summary

Sporadic colorectal cancer shows a multistep progression from normal tissue to precancerous adenomas to invasive cancer, with underlying molecular mechanisms not completely understood. Metabolomic analysis of plasma samples from colorectal cancer patients and adenoma patients identified significant differences in molecular features, including acylcarnitines, caffeine, amino acids, and bile acids. These findings provide insight into the metabolic distinctions between colorectal cancer and adenomas, potentially offering a biological interpretation of these differences.