Posts Tagged ‘tricarboxylic acid cycle’

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Conventional tumor markers are unsuitable for detecting carcinoma at an early stage and lack clinical efficacy and utility. Multiple classification analysis revealed that the variations in the levels of malonic acid and L-serine largely contributed to the separation of esophageal cancer; gastric cancer was characterized by changes in the levels of 3-hydroxypropionic acid and pyruvic acid; and L-alanine, glucuronoic lactone and L-glutamine contributed to the separation of colorectal cancer. Some metabolites are more sensitive for detecting gastrointestinal cancer than conventional biomarkers and thus metabolomics has the potential as an early diagnostic tool for cancer. Studies also showed that global metabolic profiling of colon mucosae would define metabolic signatures that not only discriminate malignant from normal mucosae, but also could distinguish the anatomical and clinicopathological characteristics of colorectal cancer. Thus it is suggested that metabolic profiling of colorectal cancer mucosae could provide new phenotypic biomarkers for colorectal cancer management.

A full spectrum of metabolic aberrations that are directly linked to colorectal cancer at early curable stages is critical for developing and deploying molecular diagnostic and therapeutic approaches that will significantly improve patient survival. A number of dysregulated metabolic pathways, such as glycolysis, tricarboxylic acid cycle, urea cycle, pyrimidine metabolism, tryptophan metabolism, polyamine metabolism, as well as gut microbial-host co-metabolism in colorectal cancer subjects are reported. Significantly increased tryptophan metabolism, and disturbed tricarboxylic acid cycle and the gut microflora metabolism were observed in the colorectal cancer patients. The urinary metabolite profile of postoperative colorectal cancer subjects altered significantly from that of the preoperative stage. The significantly down-regulated gut microflora metabolism and tricarboxylic acid cycle were observed in postoperative colorectal cancer subjects, presumably due to the colon flush involved in the surgical procedure and weakened physical conditions of the patients. The expression of 5-hydroxytryptophan significantly decreased in postsurgery cases, suggesting a recovered tryptophan metabolism toward healthy state. Abnormal histamine metabolism and glutamate metabolism were found only in the urine samples of colorectal cancer patients. There are distinct urinary metabolic footprints of colorectal cancer patients characterized by altered levels of metabolites derived from gut microbial-host co-metabolism. A panel of metabolite markers composed of citrate, hippurate, p-cresol, 2-aminobutyrate, myristate, putrescine, and kynurenate was able to discriminate colorectal cancer subjects from their healthy counterparts. These potential metabolite markers provide a novel and promising molecular diagnostic approach for the early detection of colorectal cancer.

Source References:






Read Full Post »