title: Urinary metabotyping of bladder cancer using two-dimensional gas chromatography time-of-flight mass spectrometry.
abstract: Cystoscopy is the gold standard clinical diagnosis of human bladder cancer (BC). As cystoscopy is expensive and invasive, it compromises patients' compliance toward surveillance screening and challenges the detection of recurrent BC. Therefore, the development of a noninvasive method for the diagnosis and surveillance of BC and the elucidation of BC progression become pertinent. In this study, urine samples from 38 BC patients and 61 non-BC controls were subjected to urinary metabotyping using two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS). Subsequent to data preprocessing and chemometric analysis, the orthogonal partial least-squares discriminant analysis (OPLS-DA, R2X=0.278, R2Y=0.904 and Q2Y (cumulative)=0.398) model was validated using permutation tests and receiver operating characteristic (ROC) analysis. Marker metabolites were further screened from the OPLS-DA model using statistical tests. GC×GC-TOFMS urinary metabotyping demonstrated 100% specificity and 71% sensitivity in detecting BC, while 100% specificity and 46% sensitivity were observed via cytology. In addition, the model revealed 46 metabolites that characterize human BC. Among the perturbed metabolic pathways, our clinical finding on the alteration of the tryptophan-quinolinic metabolic axis in BC suggested the potential roles of kynurenine in the malignancy and therapy of BC. In conclusion, global urinary metabotyping holds potential for the noninvasive diagnosis and surveillance of BC in clinics. In addition, perturbed metabolic pathways gleaned from urinary metabotyping shed new and established insights on the biology of human BC.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543.
authors.forename: Kishore Kumar
authors.initials: KK
authors.lastname: Pasikanti
authors.forename: Kesavan
authors.initials: K
authors.lastname: Esuvaranathan
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Hong
authors.forename: Paul C
authors.initials: PC
authors.lastname: Ho
authors.forename: Ratha
authors.initials: R
authors.lastname: Mahendran
authors.forename: Lata
authors.initials: L
authors.lastname: Raman Nee Mani
authors.forename: Edmund
authors.initials: E
authors.lastname: Chiong
authors.forename: Eric Chun Yong
authors.initials: EC
authors.lastname: Chan
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D014364:Tryptophan / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; D014364:Tryptophan; D003404:Creatinine