{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST003025","ANALYSIS_ID":"AN004960","VERSION":"1","CREATED_ON":"December 22, 2023, 12:01 am"},

"PROJECT":{"PROJECT_TITLE":"NMR- and MS-based omics reveal characteristic metabolome atlas and optimize biofluid earlydiagnostic biomarkers for esophageal squamous cell carcinoma","PROJECT_SUMMARY":"Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. We conducted NMR- and MS-based metabolomics on 1,153 matched ESCC tissues, normal mucosae, pre- and one-week post-operative sera and urines from 560 participants across three hospitals, with machine learning, logistic regression and WGCNA. Aberrations in ''alanine, aspartate and glutamate metabolism'' proved to be prevalent throughout the ESCC evolution, and were reflected in 16 serum and 10 urine metabolic signatures that were consistently identified by NMR and MS in both discovery and validation sets. NMR-based simplified panels of any five serum or urine metabolites outperformed clinical serological tumor markers (AUC = 0.984 and 0.930, respectively), and were effective in distinguishing early-stage ESCC in test set (serum accuracy = 0.994, urine accuracy = 0.879). Collectively, NMR-based biofluid screening can reveal characteristic metabolic events of ESCC and be feasible for early detection (ChiCTR2300073613).","INSTITUTE":"Radiology Department, Second Affiliated Hospital, Shantou University Medical College, Shantou","LAST_NAME":"Lin","FIRST_NAME":"Yan","ADDRESS":"No. 69, Dongxia North Road, Shantou, Guangdong, China","EMAIL":"994809889@qq.com","PHONE":"+86 18823992148"},

"STUDY":{"STUDY_TITLE":"NMR- and MS-based omics reveal characteristic metabolome atlas and optimize biofluid earlydiagnostic biomarkers for esophageal squamous cell carcinoma (part-Ⅴ)","STUDY_SUMMARY":"Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. We conducted NMR- and MS-based metabolomics on 1,153 matched ESCC tissues, normal mucosae, pre- and one-week post-operative sera and urines from 560 participants across three hospitals, with machine learning, logistic regression and WGCNA. Aberrations in ''alanine, aspartate and glutamate metabolism'' proved to be prevalent throughout the ESCC evolution, and were reflected in 16 serum and 10 urine metabolic signatures that were consistently identified by NMR and MS in both discovery and validation sets. NMR-based simplified panels of any five serum or urine metabolites outperformed clinical serological tumor markers (AUC = 0.984 and 0.930, respectively), and were effective in distinguishing early-stage ESCC in test set (serum accuracy = 0.994, urine accuracy = 0.879). Collectively, NMR-based biofluid screening can reveal characteristic metabolic events of ESCC and be feasible for early detection (ChiCTR2300073613).","INSTITUTE":"Radiology Department, Second Affiliated Hospital, Shantou University Medical College, Shantou","LAST_NAME":"Lin","FIRST_NAME":"Yan","ADDRESS":"No. 69, Dongxia North Road, Shantou, Guangdong, China","EMAIL":"994809889@qq.com","PHONE":"+86 18823992148"},

"SUBJECT":{"SUBJECT_TYPE":"Human","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"1",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"1.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"2",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"2.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"3",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"3.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"4",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"4.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"5",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"5.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"6",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"6.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"7",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"7.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"8",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"8.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"9",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"9.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"10",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"10.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"11",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"11.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"12",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"12.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"13",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"13.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"14",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"14.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"15",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"15.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"16",
"Factors":{"Fator":"Early stage ESCC"},
"Additional sample data":{"RAW_FILE_NAME":"16.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"17",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"17.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"18",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"18.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"19",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"19.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"20",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"20.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"21",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"21.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"22",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"22.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"23",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"23.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"24",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"24.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"25",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"25.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"26",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"26.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"27",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"27.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"28",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"28.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"29",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"29.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"30",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"30.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"31",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"31.CDF"}
},
{
"Subject ID":"-",
"Sample ID":"32",
"Factors":{"Fator":"Normal tissue"},
"Additional sample data":{"RAW_FILE_NAME":"32.CDF"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Tissue samples, including tumor and normal areas 5 cm away, were obtained under the guidance of experienced pathologists without compromising the patients'' pathology examinations. The collected tissue was rinsed with PBS to avoid contamination, excess moisture was removed, and it was rapidly frozen in liquid nitrogen to arrest enzymatic or chemical reactions. Samples were stored at −80°C until metabolite extraction.","SAMPLE_TYPE":"Tissue"},

"TREATMENT":{"TREATMENT_SUMMARY":"None"},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"GC-MS Analysis mainly detects seven short-chain and four medium-chain fatty acids. Qualitative and quantitative analysis was also performed using internal standard method. Metabolic extracts were analyzed using the SHIMADZU GC2030-QP2020 NX gas chromatography-mass spectrometer. The system employed an HP-FFAP capillary column, and a 1 μL aliquot of the analyte was injected in split mode (5:1). Helium was used as the carrier gas with a front inlet purge flow of 3 mL/min and a gas flow rate of 1 mL/min through the column. The initial temperature was maintained at 50 °C for 1 min, then increased to 150 °C at a rate of 50 °C/min for 1 min. Subsequently, it was raised to 170 °C at a rate of 10 °C/min for 1 min, further increased to 210 °C at a rate of 20 °C/min for 1 min, and finally raised to 240 °C at a rate of 40 °C/min for 1 min. The injection, transfer line, quad, and ion source temperatures were set at 220 °C, 240 °C, 150 °C, and 200 °C, respectively. The energy used was -70 eV in electron impact mode. Mass spectrometry data were acquired in Scan/SIM mode within the m/z range of 33-150 after a solvent delay of 3 min. Metabolite identification was performed using an in-house MS database. The pre-processing of MS raw data involved filtering individual metabolites to retain those with no more than 50% missing values. Missing values in the original data were simulated by multiplying the minimum value by a random number between 0.1 and 0.5."},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"GC","INSTRUMENT_NAME":"SHIMADZU GC2030","COLUMN_NAME":"Agilent HP5-MS (30m x 0.25mm, 0.25 um)","SOLVENT_A":"-","SOLVENT_B":"-","FLOW_GRADIENT":"-","FLOW_RATE":"350-400","COLUMN_TEMPERATURE":"475°C"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"SHIMADZU","INSTRUMENT_TYPE":"GC2030-QP2020","MS_TYPE":"EI","ION_MODE":"POSITIVE","MS_COMMENTS":"The quantitative results are calculated from the following formula: Calculation formula: C（con）= (Cs∗V1∗V3)/(M∗V2) *1000 C (con) : content of the target compound in the sample, μg/g; Cs: target compound concentration in extract, mg/l; V1: Volume of extract solution added, ML; V2: Take Out pure water supernatant volume, ML; V3: Volume of pure water added, ML; M: weighing sample, MG."},

"MS_METABOLITE_DATA":{
"Units":"m/z",

"Data":[{"Metabolite":"Acetic acid","1":"16895","2":"80995","3":"255764","4":"10518","5":"117763","6":"10413","7":"5307","8":"34952","9":"19611","10":"9695","11":"22833","12":"7365","13":"7084","14":"4847","15":"11695","16":"5257","17":"11368","18":"42027","19":"20423","20":"26580","21":"6538","22":"10384","23":"8111","24":"34435","25":"9820","26":"16873","27":"26484","28":"17005","29":"13256","30":"14265","31":"28791","32":"11242"},{"Metabolite":"Propionic acid","1":"3385","2":"19211","3":"64168","4":"995","5":"3666","6":"1110","7":"703","8":"20656","9":"3560","10":"1017","11":"5613","12":"781","13":"681","14":"778","15":"1214","16":"551","17":"791","18":"6376","19":"1768","20":"2220","21":"705","22":"902","23":"505","24":"12686","25":"1156","26":"1055","27":"1652","28":"710","29":"1002","30":"824","31":"3729","32":"899"},{"Metabolite":"Isobutyric acid","1":"6929","2":"104452","3":"88054","4":"1806","5":"75887","6":"2015","7":"1401","8":"17212","9":"14398","10":"1074","11":"1704","12":"1270","13":"2388","14":"578","15":"2819","16":"931","17":"1910","18":"31477","19":"4183","20":"2600","21":"1612","22":"1756","23":"1099","24":"10107","25":"2506","26":"2668","27":"1416","28":"1149","29":"673","30":"1011","31":"5728","32":"1430"},{"Metabolite":"Butyric acid","1":"10941","2":"164552","3":"203846","4":"3362","5":"199655","6":"2694","7":"2088","8":"21228","9":"18153","10":"2898","11":"8593","12":"3152","13":"2332","14":"1743","15":"3659","16":"1806","17":"2243","18":"28588","19":"3148","20":"1726","21":"2260","22":"1347","23":"1190","24":"6552","25":"2188","26":"1484","27":"1549","28":"1261","29":"1304","30":"1097","31":"3582","32":"1166"},{"Metabolite":"Isovaleric acid","1":"5797","2":"17218","3":"17173","4":"1319","5":"43283","6":"1169","7":"1080","8":"4458","9":"3311","10":"877","11":"1478","12":"866","13":"641","14":"592","15":"967","16":"682","17":"1294","18":"3871","19":"1131","20":"699","21":"1150","22":"725","23":"545","24":"1822","25":"1405","26":"806","27":"668","28":"648","29":"517","30":"505","31":"1662","32":"534"},{"Metabolite":"Valeric acid","1":"8977","2":"20915","3":"10773","4":"2280","5":"10343","6":"1892","7":"2116","8":"2596","9":"3558","10":"1894","11":"1568","12":"1469","13":"1157","14":"1184","15":"1105","16":"1089","17":"2100","18":"2817","19":"1399","20":"1188","21":"1642","22":"1177","23":"1030","24":"1112","25":"1838","26":"1252","27":"963","28":"884","29":"1398","30":"963","31":"944","32":"902"},{"Metabolite":"Hexanoic acid","1":"15077","2":"14516","3":"5440","4":"6322","5":"8707","6":"10865","7":"11776","8":"16160","9":"31713","10":"34469","11":"21949","12":"14021","13":"16129","14":"7766","15":"3761","16":"8985","17":"3119","18":"11061","19":"10860","20":"5157","21":"13142","22":"13676","23":"5739","24":"3366","25":"14741","26":"6746","27":"3478","28":"2929","29":"15351","30":"3264","31":"3230","32":"5037"},{"Metabolite":"Heptanoic acid","1":"963","2":"1062","3":"825","4":"801","5":"1012","6":"1022","7":"1115","8":"1022","9":"1385","10":"1293","11":"1237","12":"877","13":"968","14":"836","15":"729","16":"878","17":"624","18":"949","19":"966","20":"966","21":"992","22":"803","23":"919","24":"1041","25":"868","26":"951","27":"848","28":"818","29":"944","30":"869","31":"789","32":"625"},{"Metabolite":"Octanoic acid","1":"6344","2":"5133","3":"10934","4":"7572","5":"13973","6":"18720","7":"15324","8":"8405","9":"6115","10":"6526","11":"6128","12":"9875","13":"9290","14":"8707","15":"8767","16":"5295","17":"12558","18":"7139","19":"8367","20":"5752","21":"15894","22":"13355","23":"15437","24":"12763","25":"12029","26":"7420","27":"8173","28":"16634","29":"14296","30":"12824","31":"10801","32":"7824"},{"Metabolite":"Nonanoic acid","1":"11760","2":"15327","3":"13127","4":"12420","5":"14763","6":"9587","7":"12042","8":"12641","9":"12876","10":"19080","11":"19060","12":"16608","13":"17542","14":"13228","15":"13691","16":"10947","17":"11535","18":"14449","19":"13879","20":"14271","21":"12426","22":"12961","23":"19458","24":"15004","25":"15581","26":"13604","27":"11455","28":"15545","29":"11617","30":"14744","31":"10058","32":"17788"},{"Metabolite":"Decanoic acid","1":"2943","2":"2484","3":"4657","4":"3467","5":"5535","6":"5084","7":"5763","8":"5058","9":"3029","10":"2989","11":"3038","12":"5929","13":"4328","14":"4665","15":"5733","16":"2234","17":"5381","18":"4138","19":"3258","20":"3842","21":"7305","22":"2799","23":"5922","24":"9201","25":"7135","26":"4006","27":"3715","28":"10139","29":"6929","30":"6949","31":"6483","32":"2744"}],

"Metabolites":[{"Metabolite":"Acetic acid","CAS":"64-19-7","molecular formula":"CH3COOH","quantitated m/z":"60.05","HMDB ID":"HMDB0000042","KEGG ID":"C00033","PubChem ID":"176"},{"Metabolite":"Propionic acid","CAS":"1979/9/4","molecular formula":"CH3CH2COOH","quantitated m/z":"74.08","HMDB ID":"HMDB0000237","KEGG ID":"C00163","PubChem ID":"1032"},{"Metabolite":"Isobutyric acid","CAS":"79-31-2","molecular formula":"C4H8O2","quantitated m/z":"88.11","HMDB ID":"HMDB0001873","KEGG ID":"C02632","PubChem ID":"6590"},{"Metabolite":"Butyric acid","CAS":"107-92-6","molecular formula":"C4H8O2","quantitated m/z":"88.11","HMDB ID":"HMDB0000039","KEGG ID":"C00246","PubChem ID":"264"},{"Metabolite":"Isovaleric acid","CAS":"503-74-2","molecular formula":"C5H10O2","quantitated m/z":"102.12","HMDB ID":"HMDB0000718","KEGG ID":"C08262","PubChem ID":"10430"},{"Metabolite":"Valeric acid","CAS":"109-52-4","molecular formula":"C5H10O2","quantitated m/z":"102.13","HMDB ID":"HMDB0000892","KEGG ID":"C00803","PubChem ID":"7991"},{"Metabolite":"Hexanoic acid","CAS":"142-62-1","molecular formula":"C6H12O2","quantitated m/z":"116.16","HMDB ID":"HMDB0000535","KEGG ID":"C01585","PubChem ID":"8892"},{"Metabolite":"Heptanoic acid","CAS":"111-14-8","molecular formula":"C7H14O2","quantitated m/z":"130.18","HMDB ID":"HMDB0000666","KEGG ID":"C17714","PubChem ID":"8094"},{"Metabolite":"Octanoic acid","CAS":"124-07-2","molecular formula":"C8H16O2","quantitated m/z":"144.21","HMDB ID":"HMDB0000482","KEGG ID":"C06423","PubChem ID":"379"},{"Metabolite":"Nonanoic acid","CAS":"112-05-0","molecular formula":"C9H18O2","quantitated m/z":"158.24","HMDB ID":"HMDB0000847","KEGG ID":"C01601","PubChem ID":"8158"},{"Metabolite":"Decanoic acid","CAS":"334-48-5","molecular formula":"C10H20O2","quantitated m/z":"172.26","HMDB ID":"HMDB0000511","KEGG ID":"C01571","PubChem ID":"2969"}]
}

}