CONICET | Buscador de Institutos y Recursos Humanos

It has been suggested that colorectal cancer (CRC) cells show a distinctive metabolic organization at different development stages as in response to stress. We determined the value of metabolism reprogramming in CRC patients against controls and at different stages (I-IV) by means of bioinformatic tools. We employed 49 CRC samples from E-GEOD50421 microarray (569.593 probes specifics to human genes) and 10 controls. The informatics free access tools were: Mev4 to heat map (1.5, 2 & 2.5 fold differences); DAVID and Reactome. The study of gene expression in CRC patients versus controls revealed that this disease alters the levels of expression of genes associated with cell adhesion and proliferation that promote the cell growth and mobility. Other overexpressed genes in CRC samples correspond to prognosis, tumor diagnosis or genes closely associated to cell metabolism. Gene related to carbohydrate andlipid metabolism differed by 2 fold in CRC patients. At stages I and II our results showed a significant increase in oncogenic markers and genes of glutaminolysis, while at stage III, the significant 2 fold expression was on fatty acids pathway genes, including acyl-CoA and phosphatidylserine. At stage IV, we evidenced an increase in the expression of tetraspanin 5, CRNEP and MMP7, genes associated to cancer progress in advanced stages and metastasis. In conclusions, during the development of the disease, the metabolic pathways are reprogrammed, increasing glycolysis, glutaminolysis and fatty acid synthesis. Our results showed that CRC cells exhibit the ?Warburg Effect? at early stages (I-II) while at stage III cancer cells increase the uptake of extracellular lipids and lipoproteins, and up regulate de novo lipid biosynthesis and synthesis of cholesterol, which produce lipid metabolites for cell membranes at stage III and IV of CRC, suggesting that patients would have higher circulating levels of fatty acids than patients at early stages.