<scp>NMR</scp>‐based metabolomics combined with metabolic pathway analysis reveals metabolic heterogeneity of colorectal cancer tissue at different anatomical locations and stages

Colorectal cancer (CRC) still remains the leading cause of cancer death worldwide. This study aimed to profile the metabolic differences of colorectal cancer tissues (CCT) at different stages and sites, as compared with their distant noncancerous tissues (DNT), to investigate the temporal and spatial heterogeneities of metabolic characterization. Our NMR-based metabolomics fingerprinting revealed that many of the metabolite levels were significantly altered in CCT compared to DNT and esophageal cancer tissues, indicating deregulations of glucose metabolism, one-carbon metabolism, glutamine metabolism, amino acid metabolism, fatty acid metabolism, TCA cycle, choline metabolism, and so forth. A total of five biomarker metabolites, including glucose, glutamate, alanine, valine and histidine, were identified to distinguish between early and advanced stages of CCT. Metabolites that distinguish the different anatomical sites of CCT include glucose, glycerol, glutamine, inositol, succinate, and citrate. Those significant metabolic differences in CRC tissues at different pathological stages and sites suggested temporal and spatial heterogeneities of metabolic characterization in CCT, providing a metabolic foundation for further study on biofluid metabolism in CRC early detection.