title: Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer.
abstract: To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples.
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Guangguo
authors.initials: G
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Qin
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Meng
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D006801:Humans; D007288:Inosine / Q000097:blood; D007735:Kynuramine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D025341:Principal Component Analysis; D012372:ROC Curve; D015203:Reproducibility of Results; D013110:Sphingosine / Q000031:analogs & derivatives / Q000097:blood; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D007735:Kynuramine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D007288:Inosine; C012491:phytosphingosine; D013110:Sphingosine