{ "METABOLOMICS WORKBENCH":{"STUDY_ID":"ST001662","ANALYSIS_ID":"AN002713","VERSION":"1","CREATED_ON":"January 26, 2021, 11:32 am"}, "PROJECT":{"PROJECT_TITLE":"Urinary LCMS metabolimc study in bladder cancer","PROJECT_SUMMARY":"Bladder cancer (BC) is among the most frequent malignancies worldwide. Novel non-invasive markers are needed to diagnose and stage BC with more accuracy than invasive procedures such as cystoscopy. Our aim was to discover novel urine metabolomic profiles to diagnose and stage non-muscle invasive (NMIBC) and muscle-invasive (MIBC) patients using ultra-performance liquid chromatography analysis (UPLC)-based metabolomics. We prospectively recruited 64 BC patients (19 TaG1, 11 TaG3, 20 T1G3, 12 T2G3, 1 T2G2, 1 T3G3) and 20 age- and sex-matched healthy volunteers without evidence of renal or bladder condition confirmed by ultrasound, from whom we collected a first morning urine sample (before surgery in patients). We conducted a UPLC-quadrupole-time-of-flight mass spectrometry (UPLC-Q-ToF MS) untargeted metabolomic analysis in all urine samples. We selected the discriminant variables between groups with a supervised orthogonal-least-squares discriminant analysis (OPLS-DA) analysis and we identified them by querying their exact mass against those presented in online databases through a mediator platform. Subsequently, we confirmed the dysregulated metabolites when chemical standards were commercially available. We compared all clinical groups of patients with controls and we identified dysregulated metabolites in every comparison. Of these, we confirmed p-cresol glucuronide as potential diagnostic biomarker, and potential staging tool for NMIBC patients. Among NMIBC patients, we identified p-coumaric acid as a potential staging biomarker for milder NMIBC stages (TaG1). Additionally, we confirmed spermine and adenosine as potential staging biomarkers for MIBC. This is the first study conducted in urine samples of most stages of NMIBC and MIBC and healthy controls to identify non-invasive biomarkers. Once confirmed, these may improve BC management thus reducing the use of current harmful diagnostic techniques.","INSTITUTE":"Health Research Institute Hospital La Fe","LABORATORY":"Analytical Unit","LAST_NAME":"Roca Marugán","FIRST_NAME":"Marta","ADDRESS":"Avenida Fernando Abril Martorell 106, Torre A, Valencia, Valencia, 46026, Spain","EMAIL":"marta_roca@iislafe.es","PHONE":"680888576"}, "STUDY":{"STUDY_TITLE":"LC-MS Metabolomics of Urine Reveals Distinct Profiles for Low- and High-Grade Bladder Cancer","STUDY_SUMMARY":"Bladder cancer (BC) is among the most frequent malignancies worldwide. Novel non-invasive markers are needed to diagnose and stage BC with more accuracy than invasive procedures such as cystoscopy. Our aim was to discover novel urine metabolomic profiles to diagnose and stage non-muscle invasive (NMIBC) and muscle-invasive (MIBC) patients using ultra-performance liquid chromatography analysis (UPLC)-based metabolomics. We prospectively recruited 64 BC patients (19 TaG1, 11 TaG3, 20 T1G3, 12 T2G3, 1 T2G2, 1 T3G3) and 20 age- and sex-matched healthy volunteers without evidence of renal or bladder condition confirmed by ultrasound, from whom we collected a first morning urine sample (before surgery in patients). We conducted a UPLC-quadrupole-time-of-flight mass spectrometry (UPLC-Q-ToF MS) untargeted metabolomic analysis in all urine samples. We selected the discriminant variables between groups with a supervised orthogonal-least-squares discriminant analysis (OPLS-DA) analysis and we identified them by querying their exact mass against those presented in online databases through a mediator platform. Subsequently, we confirmed the dysregulated metabolites when chemical standards were commercially available. We compared all clinical groups of patients with controls and we identified dysregulated metabolites in every comparison. Of these, we confirmed p-cresol glucuronide as potential diagnostic biomarker, and potential staging tool for NMIBC patients. Among NMIBC patients, we identified p-coumaric acid as a potential staging biomarker for milder NMIBC stages (TaG1). Additionally, we confirmed spermine and adenosine as potential staging biomarkers for MIBC. This is the first study conducted in urine samples of most stages of NMIBC and MIBC and healthy controls to identify non-invasive biomarkers. Once confirmed, these may improve BC management thus reducing the use of current harmful diagnostic techniques.","INSTITUTE":"Health Research Institute Hospital La Fe","LABORATORY":"Analytical Unit","LAST_NAME":"Roca Marugán","FIRST_NAME":"Marta","ADDRESS":"Avenida Fernando Abril Martorell 106, Torre A, Valencia, Valencia, 46026, Spain","EMAIL":"marta_roca@iislafe.es","PHONE":"680888576"}, "SUBJECT":{"SUBJECT_TYPE":"Human","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606","GENDER":"Pooled"}, "SUBJECT_SAMPLE_FACTORS":[ { "Subject ID":"-", "Sample ID":"mv08618_05.mzXML", "Factors":{"Disease":"QC","Type of tumor":"QC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_05.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_08.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_08.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_09.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_09.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_11.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_11.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_12.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_12.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_13.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_13.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_14.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_14.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_15.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_15.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_16.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_16.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_17.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_17.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_18.mzXML", "Factors":{"Disease":"QC","Type of tumor":"QC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_18.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_19.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_19.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_20.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_20.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_21.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_21.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_22.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_22.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_23.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_23.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_24.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_24.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_25.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_25.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_26.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_26.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_27.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_27.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_28.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_28.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_29.mzXML", "Factors":{"Disease":"QC","Type of tumor":"QC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_29.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_31.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_31.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_32.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_32.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_33.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_33.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_34.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_34.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_35.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_35.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_36.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_36.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_37.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_37.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_38.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_38.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_39.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_39.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_40.mzXML", "Factors":{"Disease":"QC","Type of tumor":"QC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_40.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_41.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_41.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_42.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_42.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_43.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_43.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_44.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_44.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_45.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_45.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_46.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_46.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_47.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_47.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_48.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_48.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_49.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_49.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_50.mzXML", "Factors":{"Disease":"QC","Type of tumor":"QC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_50.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_51.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_51.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_52.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_52.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_53.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_53.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_54.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_54.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_55.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_55.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_56.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_56.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_57.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_57.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_58.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_58.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_59.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_59.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_60.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_60.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_61.mzXML", "Factors":{"Disease":"QC","Type of tumor":"QC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_61.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_62.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_62.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_63.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_63.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_64.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_64.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_65.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_65.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_66.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_66.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_67.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_67.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_68.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_68.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_69.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_69.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_70.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_70.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_71.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_71.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_72.mzXML", "Factors":{"Disease":"QC","Type of tumor":"QC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_72.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_73.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_73.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_74.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_74.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_75.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_75.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_76.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_76.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_77.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_77.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_78.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_78.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_79.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_79.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_80.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_80.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_81.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_81.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_82.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_82.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_83.mzXML", "Factors":{"Disease":"QC","Type of tumor":"QC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_83.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_84.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_84.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_85.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_85.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_86.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_86.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_87.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_87.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_88.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_88.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_89.mzXML", "Factors":{"Disease":"T2G3","Type of tumor":"MIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_89.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_90.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_90.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_91.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_91.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_93.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_93.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_94.mzXML", "Factors":{"Disease":"QC","Type of tumor":"QC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_94.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_95.mzXML", "Factors":{"Disease":"TAG3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_95.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_96.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_96.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_97.mzXML", "Factors":{"Disease":"TAG1","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_97.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_98.mzXML", "Factors":{"Disease":"Control","Type of tumor":"Control"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_98.mzXML"} }, { "Subject ID":"-", "Sample ID":"mv08618_99.mzXML", "Factors":{"Disease":"T1G3","Type of tumor":"NMIBC"}, "Additional sample data":{"RAW_FILE_NAME":"mv08618_99.mzXML"} } ], "COLLECTION":{"COLLECTION_SUMMARY":"Study subjects Sixty-four BC patients were recruited between May 2016 and April 2018 at La Fe University and Polytechnic Hospital (Valencia, Spain). Twenty age- and sex-matched healthy volunteers (control group) who underwent an ultrasound scan to rule out the presence of urological malignancies or other alterations were also recruited. Patients and controls were clinically followed-up until May 2020. Pre-operative clinical staging was performed through physical examination, urine cytology and CT scans of the chest, abdomen and pelvis (in case of invasive bladder cancer). The tumor histological classification was done according to grade in the WHO 1973 and 2004 classifications. Demographic and clinical data were collected. The exclusion criteria were lack of informed consent, absence of histological confirmation and presence of other malignancies. Informed consent was obtained from all participants according to protocols approved by the ethics review board at La Fe University and Polytechnic Hospital. The study was performed according to the declaration of Helsinki, as amended in Edinburgh in 2000. Urine collection A first morning urine sample of 25-50 ml was collected in sterile containers from all participants. Urine was kept at 4 ºC until processing and centrifuged at 805 x g for 5 min at 4 ºC to remove cellular debris. Supernatant was aliquoted and frozen at -80 ºC until analyzed. The concentration of creatinine in each urine sample was measured by clinical laboratory standardized methods.","SAMPLE_TYPE":"Urine"}, "TREATMENT":{"TREATMENT_SUMMARY":"A first morning urine sample of 25-50 ml was collected in sterile containers from all participants. Urine was kept at 4 ºC until processing and centrifuged at 805 x g for 5 min at 4 ºC to remove cellular debris. Supernatant was aliquoted and frozen at -80 ºC until analyzed. The concentration of creatinine in each urine sample was measured by clinical laboratory standardized methods"}, "SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Sample treatment was performed according to a previous study 22. Briefly, after centrifugation, 40 µl of urine cleaned supernatant were transferred to a 96 well-plate for LC-MS (liquid chromatography-mass spectrometry) analysis and diluted by adding 50 µl of H2O (0.1 % v/v HCOOH). Each sample was spiked with 10 µl of 20 µM IS solution containing phenylalanine-d5, caffeine-d9, leukine enkephaline and reserpine in H2O:CH3OH (1:1, 0.1% v/v HCOOH). Blank samples were prepared by replacing urine by ultrapure H2O. A quality control (QC) sample was prepared by mixing 10 µl from each urine sample."}, "CHROMATOGRAPHY":{"CHROMATOGRAPHY_SUMMARY":"The metabolomic analysis was carried out using an Ultra-Performance Liquid Chromatography (UPLC) system coupled to an iFunnel Q-ToF (quadrupole-time-of-flight) Agilent 6550 mass spectrometer (Agilent Technologies, CA, USA) using an UPLC BEH C18 (100 x 2.1 mm, 1.7 µm, Waters, Wexford, Ireland) column from Waters (Wexford, Ireland). Autosampler and column temperatures were set to 4 °C and 40 °C, respectively, and the injection volume was 5 µl. Mobile phase A and mobile phase B consisted of H2O and acetonitrile, both containing 0.1% of formic acid. A gradient elution was performed at a flow rate of 400 µl min-1 along 14 min as follows: initial conditions of 98% of mobile phase A was maintained for 1 min, and then decreased until 75% in 2 min, 50% in 3 min and 5% in 3 more min. 95% of mobile phase B was held for 3 min and then, a 0.55 min gradient was used to return to the initial conditions, which were held for 2.5 min to totally column recovery.","CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Agilent 6550","COLUMN_NAME":"Waters Acquity BEH C18 (100 x 2mm, 1.7um)"}, "ANALYSIS":{"ANALYSIS_TYPE":"MS"}, "MS":{"INSTRUMENT_NAME":"Agilent 6550 QTOF","INSTRUMENT_TYPE":"QTOF","MS_TYPE":"EI","ION_MODE":"POSITIVE","MS_COMMENTS":"Full scan MS data from 50 to 1700 m/z with a scan frequency of 6 Hz was collected both in positive (ESI+) and negative (ESI-) electrospray ionization modes. The following electrospray ionization parameters were used: gas temperature, 200 °C; drying gas, 14 l min-1; nebulizer, 60 psi; sheath gas temperature, 350 °C; sheath gas flow, 11 l min-1. Urine samples were randomly injected in the chromatographic system in order to avoid intra-batch variability, as well as to enhance quality and reproducibility. QC sample was analyzed every 7 injections to monitor and correct changes in the instrument response. QC sample was also repeatedly analysed under auto MS/MS and All-ion (MSE) fragmentation modes to provide useful information of fragment ions for identification purposes. Sample stability and analytical drift were investigated through IS intensities. Blank analysis was performed at the end of the sequence and used to identify artefacts from sampling, preparation of samples and analysis.","MS_RESULTS_FILE":"ST001662_AN002713_Results.txt UNITS:peak area Has m/z:Yes Has RT:Yes RT units:Seconds"} }