title: Distinct urinary metabolic profile of human colorectal cancer.
abstract: A full spectrum of metabolic aberrations that are directly linked to colorectal cancer (CRC) at early curable stages is critical for developing and deploying molecular diagnostic and therapeutic approaches that will significantly improve patient survival. We have recently reported a urinary metabonomic profiling study on CRC subjects (n = 60) and health controls (n = 63), in which a panel of urinary metabolite markers was identified. Here, we report a second urinary metabonomic study on a larger cohort of CRC (n = 101) and healthy subjects (n = 103), using gas chromatography time-of-flight mass spectrometry and ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry. Consistent with our previous findings, we observed a number of dysregulated metabolic pathways, such as glycolysis, TCA cycle, urea cycle, pyrimidine metabolism, tryptophan metabolism, polyamine metabolism, as well as gut microbial-host co-metabolism in CRC subjects. Our findings confirm distinct urinary metabolic footprints of CRC patients characterized by altered levels of metabolites derived from gut microbial-host co-metabolism. A panel of metabolite markers composed of citrate, hippurate, p-cresol, 2-aminobutyrate, myristate, putrescine, and kynurenate was selected, which was able to discriminate CRC subjects from their healthy counterparts. A receiver operating characteristic curve (ROC) analysis of these markers resulted in an area under the receiver operating characteristic curve (AUC) of 0.993 and 0.998 for the training set and the testing set, respectively. These potential metabolite markers provide a novel and promising molecular diagnostic approach for the early detection of CRC.
authors.affiliation: Department of Chemistry, East China Normal University, Shanghai 200062, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.forename: Tianlu
authors.initials: T
authors.lastname: Chen
authors.forename: Yunping
authors.initials: Y
authors.lastname: Qiu
authors.forename: Xia
authors.initials: X
authors.lastname: Zou
authors.forename: Minhua
authors.initials: M
authors.lastname: Zheng
authors.forename: Binbin
authors.initials: B
authors.lastname: Tan
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.forename: Taotao
authors.initials: T
authors.lastname: Dong
authors.forename: Pingang
authors.initials: P
authors.lastname: He
authors.forename: Linjing
authors.initials: L
authors.lastname: Zhao
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhao
authors.forename: Lisa X
authors.initials: LX
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D025341:Principal Component Analysis; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor