Research Of Tissue Metabolomics In Colorectal Cancer

Cancer is a serious disease that threatens to human's life and health,and colorectal cancer(CRC),as a common gastrointestinal malignancy disease,is a serious threat to people's health.Metabolomics,as a new discipline in recent years,is used in biological research increasingly to identify markers related to disease diagnosis or to identify specific mechanisms for the occurrence of disease.Based on the high incidence of colorectal cancer and mortality,in-depth study of the pathogenesis of colorectal cancer is of great significance on its early diagnosis and prevention.Based on the UPLC-MS platform,the metabolic profilings of 87 colorectal cancer tissues(51 cases of cancer tissues and 36 cases of paired tissues samples)was obtained and the metabolic profiles of the samples were analyzed by principal component analysis(PCA).Then,the PLS-DA model was used to screen and identify the different metabolites.After obtaining stable and reliable metabolites,metabolic pathway analysis were established.For rectal cancer and adjacent tissues,there are 14 different metabolites were screened and identified,in which taurine,xanthine,amino acid and acylcarbamate were up-regulated and the guanine nucleoside was down-regulated.Colon cancer and adjacent tissue identified amino acids,acyl carnitine and its derivatives a total of 18 different metabolites,metabolic pathway analysis found that amino acid metabolism may be associated with the occurrence of colon cancer.This result suggests that the occurrence of colorectal cancer is closely related to energy metabolism,and the occurrence of rectal cancer tends to changes of ? oxidation,colon cancer tends to TCA cycle's imbalance.Then,analysis based on the age of the patients showed two different metabolites including lysine and succinic acid were upregulated in the group of patients older than 70 years.The screening and identification of different metabolites between left and right colon tissues found that 16 differential metabolites including phosphatidylcholine,phosphatidylethanolamine,amino acids and their derivatives were changed.Metabolic pathway analysis showed that phenylalanine metabolic pathway were changed.Analysis of left and right colon cancer tissue found 7 differential metabolites,including amino acids and carnitine.The pathways associated with these seven differential metabolites are mainly purine metabolic pathways.Then,the characteristic differential metabolites between the left and right colon cancer and adjacent tissues were identified.The results showed that citicoline,hydroxysuccinic acid and hypoxanthine were significantly up-regulated in the left colon cancer,and the uric acid was significantly decreased.While the carnityl carnitine and hypoxanthine was specific up-regulated in right colon cancer.By comparing the metabolites of three different colorectal cancer,taurine was found to increase significantly in all three type colorectal cancer.And glutamate was increased significantly in the left colon and rectal cancer,indicating that these changes of metabolites are closely related to the occurrence of colorectal cancer.In this study,through the established metabolic profile analysis platform based on LC-MS,the metabolic profile of colorectal cancer tissue under the influence of different factors was analyzed systematically,and the metabolites of the differences between different groups were screened and identified,established the research foundation for the deep research on metabolic biomarkers and related mechanism of colorectal cancer.