title: Urinary metabolite profiling combined with computational analysis predicts interstitial cystitis-associated candidate biomarkers.
abstract: Interstitial cystitis/painful bladder syndrome (IC) is a chronic syndrome of unknown etiology that presents with bladder pain, urinary frequency, and urgency. The lack of specific biomarkers and a poor understanding of underlying molecular mechanisms present challenges for disease diagnosis and therapy. The goals of this study were to identify noninvasive biomarker candidates for IC from urine specimens and to potentially gain new insight into disease mechanisms using a nuclear magnetic resonance (NMR)-based global metabolomics analysis of urine from female IC patients and controls. Principal component analysis (PCA) suggested that the urinary metabolome of IC and controls was clearly different, with 140 NMR peaks significantly altered in IC patients (FDR < 0.05) compared to that in controls. On the basis of strong correlation scores, fifteen metabolite peaks were nominated as the strongest signature of IC. Among those signals that were higher in the IC group, three peaks were annotated as tyramine, the pain-related neuromodulator. Two peaks were annotated as 2-oxoglutarate. Levels of tyramine and 2-oxoglutarate were significantly elevated in urine specimens of IC subjects. An independent analysis using mass spectrometry also showed significantly increased levels of tyramine and 2-oxoglutarate in IC patients compared to controls. Functional studies showed that 2-oxoglutarate, but not tyramine, retarded growth of normal bladder epithelial cells. These preliminary findings suggest that analysis of urine metabolites has promise in biomarker development in the context of IC.
authors.affiliation: College of Pharmacy, Seoul National University , Seoul 151-724, Korea.
authors.forename: He
authors.initials: H
authors.lastname: Wen
authors.forename: Tack
authors.initials: T
authors.lastname: Lee
authors.forename: Sungyong
authors.initials: S
authors.lastname: You
authors.forename: Soo-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Hosook
authors.initials: H
authors.lastname: Song
authors.forename: Karyn S
authors.initials: KS
authors.lastname: Eilber
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Anger
authors.forename: Michael R
authors.initials: MR
authors.lastname: Freeman
authors.forename: Sunghyouk
authors.initials: S
authors.lastname: Park
authors.forename: Jayoung
authors.initials: J
authors.lastname: Kim
mesh_terms: D015415:Biomarkers / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D019295:Computational Biology / Q000379:methods; D018856:Cystitis, Interstitial / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D025341:Principal Component Analysis; D056910:Republic of Korea
chemical_list: D015415:Biomarkers
keywords: Metabolomics; NMR; biomarker; bladder; interstitial cystitis; metabolites