GC/MS and LC/MS-based Tissue Metabolomic Analysis Detected Increased Levels of Antioxidant Metabolites in Colorectal Cancer.

Late-stage colorectal cancer is resistant to current treatments. Understanding the biological processes responsible for the development and progression of colorectal cancer could aid the development of new diagnostic and treatment approaches. We used gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry-based metabolomic analysis to measure metabolite levels in pairs of colorectal cancer tissue samples and samples of the adjacent macroscopically normal mucosal tissue from 10 colon cancer patients. Regarding nucleotide metabolomic intermediates, the colorectal cancer tissue contained lower levels of ribulose 5-phosphate and higher levels of xanthine, adenine, and hypoxanthine than the normal tissue. The levels of antioxidant metabolites, such as sulfur-containing amino acids, were also significantly higher in the colorectal cancer tissue. The level of tryptophan was decreased, and the levels of molecules downstream of the tryptophan pathway, such as kynurenine and quinolinic acid, which protect colorectal cancer against the host's immune system and function in de novo nicotinamide adenine dinucleotide synthesis, were increased in the colorectal cancer tissue. The colorectal cancer tissue samples also contained higher levels of lysophospholipids and fatty acids, especially stearic acid and polyunsaturated fatty acids, including arachidonic acid and docosahexaenoic acid. Thus, understanding these cancer-specific alterations could make it possible to detect colorectal cancer early and aid the development of additional treatments for the disease, leading to improvements in colorectal cancer patients' quality of life.