Research On A Diagnostic Model Of Renal And Bladder Cancer Based On Urine Metabolomics

ObjectivesThe purpose is to establish urine metabolite diagnostic models for renal cell carcinoma and bladder cancer by metabolomics technology and to explore the abnormal metabolic pathways in the tumorigenesis of renal cell carcinoma and bladder cancer.Methods403 urine samples were collected,including healthy control group,renal cell carcinoma group and bladder cancer group(including with or without microscopic hematuria respectively).The metabolites of urine samples were detected by ultra-performance liquid chromatography-mass spectrometry platform.The urine samples of cancer group(including renal cancer and bladder cancer)and healthy control group were analyzed,and the metabolite diagnostic model of cancer group was established and verified externally.The urine samples of bladder cancer and renal cell carcinoma(with or without microscopic hematuria)were analyzed respetively,and the metabolite diagnostic models were established accordingly.Based on the differential metabolites,we explored the altered metabolic pathways in renal cell carcinoma and bladder cancer.ResultsThrough the analysis of the data,three sets of metabolite diagnostic models were established.Firstly,the diagnostic model of the cancer group was composed of α-CEHC,β-cortolone,deoxyinosine,flunisolide,11b,17a,21-trihydroxypreg-nenolone and glycerol tripropanoate.The area under ROC curves in the discovery group were 0.950 and 0.867 in the external validation group.Metabolic pathway analysis indicated that lipid metabolism was up-regulated,while purine metabolism was down regulated.Secondly,the diagnostic model of bladder cancer vs renal cell carcinoma group without hematuria consists of 4-ethoxymethylphenol,prostaglandin F2b,thromboxane B3,hydroxybutyrylcarnitine,3-hydroxyphloretin and N’-formylkynurenine.The area under ROC curves in the discovery group were 0.829 and 0.76 in the external validation group.Thirdly,the diagnostic model of bladder cancer vs renal cell cancer group with hematuria was composed of 1-hydroxy-2-oxopropyl tetrahydropterin,1-acetoxy-2-hydroxy-16-hep-tadecyn-4-one,1,2-dehydrosalsolinol and L-tyrosine.The area under ROC curve was 0.913.Metabolic pathway analysis demonstrated that there was significant difference in amino acid and purine metabolism between renal cell carcinoma and bladder cancer group with hematuria.ConclusionBased on the analysis of metabonomics,three models of urinary metabolite tumor markers were established.The model can distinguish cancer patients from healthy persons,renal cell caricnoma from bladder cancer patients.Through the analysis of metabolic pathway,the metabolic abnormalities of renal cancer and bladder cancer were explained,which could provide a reference for finding new drug targets.