Metabolomics Of Gastric Cancer, Colorectal Cancer, And Pancreatic Cancer Urine By Capillary Electrophoresis Mass Spectrometry Based On Moving Reaction Boundary

AIM: Gastrointestinal cancer is the common malignancy in the world especially inthe developing countries. In China, gastric cancer is the second cause of cancer-associateddeath. The early diagnosis of gastrointestinal tumors is very difficult because of lack of thetypical clinical manifestations and symptoms in the early stage, so most of them wereidentified in the advanced stage. People’s quality of life and the survival time wereseriously affected by the metastasis and recurrence, high mortality, and poor prognosis oftumors. Therefore, early diagnosis and early treatment is especially important forimproving the quality of life and prolonging survival time of patients with gastrointestinaltumors. Currently, the methods to diagnose gastrointestinal cancer mainly rely on digestiveendoscopy and biopsy pathology, which is relatively mature and reliable, but the accuracyof diagnosis is affected significantly by human factors(such as the experience of theandoscopists), and also limited by its invasive nature, that is why we need to explore moreaccurate and reliable method to screen gastrointestinal tumor early. In recent years,metabolomics has been developed unprecedentedly with the development of genomics andproteomics, especially in the field of analysis of metabolites in body fluids of tumorpatients. Metabonomics takes body fluids and tissues of animals as objects to study thedynamic changes of the quality and quantity of metabolites produced by the organismsunder pathophysiological stimuli or genetic modification, and concerns the smallmolecules with molecular weight less than1000Da. CE-MS is widely used in clinicaltesting for target metabolites analysis because of the advantages of less sample requirement,high resolution, good detection selectivity, short analysis time and easy operation. In this study, we detected free amino acids and organic acids metabolic profilings of gastric acncer,colorectal cancer and pancreatic cancer patients to investigate the variation and theirclinical significance of the metabolism of amino acids and organic acids in the urine ofpatients with gastrointestinal tumors.METHODS: The morning urinary samples of patients with gastric cancer, colorectalcancer, pancreatic cancer and healthy adults were collected and divided into the cancergroup and normal control group, respectively. The profiles of free amino acids and organicacids in urine were analyzed by capillary electrophoresis mass spectrometry. Statisticalanalysis was used to analyze the data with SPSS17.0combined with the qualitative andquantitative analysis of20kinds of amino acids and9kinds of organic acids standard.Principal component analysis was performed to observe the metabolic information and toestablish the diagnostic models of gastric cancer, colorectal cancer, and pancreatic cancer.RESULTS:1. There were significant changes in urine metabolic profiling of gastriccancer patients compared with non-gastric cancer group(normal group): compared withnormal group, the levels of leucine, isoleucine, valine, arginine, and lactate in the urine ofgastric cancer increased(p<0.05), while the levels of histidine, methionine, aspartic acids,serine, succinic acid, citric acid and malic acid decreased(p<0.05); the levels of valine andisoleucine were decreased (p<0.05) in the advanced gastric cancer group compared withthe early stage gastric cancer.2. There was significant difference in urine metabolismbetween colorectal cancer group and normal group: compared with the normal group,arginine, leucine, isoleucine, valine and lactic acid in the urine of colorectal cancer groupwere up-regulated (p<0.05), while histidine, methionine, serine, aspartic acid, malic acid,succinic acid and citric acid were down-regulated (p<0.05); the concentration of valine andisoleucine decreased (P<0.05) in the urine of adcancer colorectal cancer group comparedwith the early stage colorectal cancer.3. The urine metabolites were also expresseddifferentially between pancreatic cancer and normal group: the levels of arginine, leucine,valine, isoleucine, and lactate increased (P<0.05) while the levels of methionine, serine,succinic acid, citric acid and malic acid decreased (P<0.05) in pancreatic cancer group. CONCLUSION: The capillary electrophoresis mass spectrometry based on MRB canrelatively better reveal the urinary metabolic information in gastric cancer, colorectalcancer, pancreatic cancer, and normal group, so it is feasible. We filtered out amino acidsand organic acids of certain diagnostic significance. The results suggest that this methodmay have a reference value in the diagnosis of gastric cancer, colorectal cancer andpancreatic cancer and deserves further study.