| Background Malnutrition is a common problem for cancer patients,and it is more common in gastric cancer,pancreatic cancer,esophageal cancer,primary lung cancer,colorectal cancer and so on.There is a high incidence of nutritional risk and malnutrition in cancer patients in China,Significantly,more malnutrition incidence occured in patients with advanced cancer.Malnutrition runs through the entire course of tumor occurrence and development,seriously jeopardizing the treatment sresponse of tumor patients.The malnutrition of cancer patients is gradually getting the attention of the clinical oncology industry.Scientific and reasonable tumor nutrition management is inseparable from precise nutritional diagnosis.However,the current diagnosis of malnutrition in cancer patients has a low penetration rate.The current nutritional diagnosis focuses on the classification of the degree of malnutrition,which lacks the type and content of nutrients as the basis Classification and diagnostic criteria.In this study,metabolomics analysis of plasma samples from patients with non-digestive system tumors was performed by ultra-high performance liquid chromatography tandem mass spectrometry(UPLC)to explore the metabolic differences of tumor patients with different nutritional status,and to discover potential specific small molecular metabolites,with a view to A better understanding of the metabolic mechanism of tumor malnutrition provides a basis for formulating more precise nutritional and metabolic treatments.Objective Clarify the differences in plasma nutrients in patients with non-digestive system malignancies with different nutritional status Looking for specific metabolites and metabolic pathways for malnourished patientsMethods The case data of patients with non-digestive tract malignant tumors in the Department of Oncology Nutrition and Metabolism,Anhui Provincial Hospital from June 2020 to December 2020.Inclusion criteria:(1)Hospitalized patients with nondigestive malignant tumors confirmed by histopathology or cytology;(2)Age ≥18 years;(3)Expected survival ≥2 months;(4)Prolongation of Prothrombin time(PT)≤2.5 s;(5)Without receiving intravenous infusion of fat emulsion and amino acids within 3 days before collection.According to the PG-SGA,all selected subjects were divided into: non(mild)malnutrition group(n=33)and severe malnutrition group(n=17).Collect the clinical data of the patients,and use ultra-high performance liquid chromatography tandem mass spectrometry(UPLC)to detect the serum samples of the enrolled patients,and obtain the raw mass spectrometry data of different nutritional status groups.Import the data into the SIMCA software,and perform t-test,principal component analysis,partial least squares-discriminant analysis and orthogonal filtering partial least squares-discriminant analysis on the data respectively to obtain the different metabolites of different nutritional status groups,and consult the database Analyze the differential metabolic pathway.Results A total of 50 patients were enrolled,of which 33 were in the non-(mild)malnutrition group and 17 were in the severe malnutrition group.The age of the severe malnutrition group was significantly higher than that of the non(mild)malnutrition group,and the fasting body weight,BMI,serum albumin,prealbumin,neutrophil count,and lymphocyte count were significantly lower than those of the non(mild)malnutrition group In the two groups,there was no significant difference in hemoglobin,fasting blood glucose,total cholesterol,triglyceride,and white blood cell count between the two groups(P>0.05).In physical examination,the muscle mass and basal metabolic rate of the severely malnourished group were lower than those of the non-(mild)malnourished group,with statistically significant differences(P<0.05),and no significant difference in body fat mass(P>0.05).In terms of inflammation indicators,the normal rate of inflammation indicators in the severe malnutrition group was CRP 33.3%,PCT 40%,and IL-6 36.7%,which were lower than those in the non-(mild)malnutrition group(CRP 75%,PCT 87.25%,IL-6 56.25%),in which CRP(χ2=7.26,P=0.007)and the normal rate of PCT(χ2=9.58,P=0.002)have statistically significant differences.Results in Metabolomics: 1.In the positive and negative ion OPLS-DA model,the severely malnourished group and the non-(mild)malnourished group samples are significantly separated,indicating that the two groups have significant metabolic differences in plasma levels.2.A total of 57 different metabolites were found between two groups,of which the level of 26 substances decreased in the severely malnourished group,and the level of 31 substances increased.Compared with the no(mild)malnutrition group,the severely malnourished group had lower concentrations of piperine,lignin acid,deoxycholic acid,glyceryl monostearate,hyodeoxycholic acid,and chenodeoxycholic acid,cholic acid,hyocholic acid,FA(18:2;2O),PC(36:4),LPC(18:2),PC(38:3),Uridine,N-Acetylarginine,arabinofuranosyl uracil,indole acetaldehyde,2-ketoglutarate,tryptophan,Lyso PA(0:0/18:0),Lyso PA(18:2/0:0),uracil,glutamic acid,Lyso PA(18:0/0:0),3-indole acrylic acid(IAA),indole-3-formaldehyde,Lyso PA(20:3/0:0);3-methoxytyrosine,SM(d18:1/16:0),SM(d17:1/16:0),PC(16:0 /16:0),glyceric acid,SM(d18:0/16:0),sebacic acid,SM(d42:3),symmetric dimethylarginine,SM(d18:2/16: 0),oleic acid,deoxycarnitine,PC(O-18:1/16:0),SM(d18:2/18:0),Oleoylcarnitine.The severely malnourished group had lower concentrations of SM(d18:1/18:0),2-hydroxyisovaleric acid,FA(16:1;2O),PC(O-16: 0/18:2),acetylcarnitine,2-hydroxymyristoylcarnitine,9-hexadecylcarnitine,D- glucuronic acid,3-hydroxybutyric acid,threonic acid,tryptophan 2-C-Mannoside,erucic acid,capric acid,6-hydroxyhexanoic acid,2-hydroxyvaleric acid,3-hydroxybutyrylcarnitine.3.The differences in the metabolic pathways of non-digestive tumor patients with different nutritional status mainly involve 14 metabolic pathways: butyrate metabolism,D-glutamine and D-glutamate metabolism,arginine synthesis,and glycerophospholipid metabolism,Glyceride metabolism,ketone body synthesis and decomposition,linoleic acid metabolism,alanine,aspartic acid and glutamic acid metabolism,nitrogen metabolism,glyoxylic acid and dicarboxylate metabolism,ascorbic acid and alginate metabolism,Pyrimidine metabolism,tryptophan metabolism,primary bile acid synthesis.Conclusion The severely malnourished group and the non-(mild)malnourished group have significant differences in the level of plasma metabolome.Compared with the non(mild)malnutrition group,the severe malnutrition group had metabolic abnormalities such as amino acid metabolism,fatty acid metabolism,and glycerophospholipid metabolism.It may be closely related to the symptoms of malnutrition,skeletal muscle atrophy,and tumor progression. |
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