Limits...
Urinary metabolite profiling combined with computational analysis predicts interstitial cystitis-associated candidate biomarkers.

Wen H, Lee T, You S, Park SH, Song H, Eilber KS, Anger JT, Freeman MR, Park S, Kim J - J. Proteome Res. (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Seoul National University , Seoul 151-724, Korea.

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.

Show MeSH

Related in: MedlinePlus

1H NMR spectra of urine samplesderived from controls(Ctrl, A) and IC subjects (IC, B). Metabolite peaks were assignedas described in Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4286193&req=5

fig1: 1H NMR spectra of urine samplesderived from controls(Ctrl, A) and IC subjects (IC, B). Metabolite peaks were assignedas described in Materials and Methods.

Mentions: Because analysis of urine metabolites is a promising,noninvasive approach to study bladder disease, as shown with bladdercancer,17 we investigated the metaboliteprofile of the individual urine samples using 1H NMR spectroscopy.An NMR spectrometer equipped with a triple-resonance cryogenic probewas used for the analysis. NMR-based metabolomics requires relativelysimple sample preparation and provides structural information on metabolites.Our analysis and data requisition resulted in a total of 4501 metabolitesdetected. The spectra featured visually identifiable differences inthe signal ranges of 6.5–7.5, 3.5–4.0, and 2.0–2.5ppm, suggesting metabolic differences between IC patients and controls(Figure 1).


Urinary metabolite profiling combined with computational analysis predicts interstitial cystitis-associated candidate biomarkers.

Wen H, Lee T, You S, Park SH, Song H, Eilber KS, Anger JT, Freeman MR, Park S, Kim J - J. Proteome Res. (2014)

1H NMR spectra of urine samplesderived from controls(Ctrl, A) and IC subjects (IC, B). Metabolite peaks were assignedas described in Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4286193&req=5

fig1: 1H NMR spectra of urine samplesderived from controls(Ctrl, A) and IC subjects (IC, B). Metabolite peaks were assignedas described in Materials and Methods.
Mentions: Because analysis of urine metabolites is a promising,noninvasive approach to study bladder disease, as shown with bladdercancer,17 we investigated the metaboliteprofile of the individual urine samples using 1H NMR spectroscopy.An NMR spectrometer equipped with a triple-resonance cryogenic probewas used for the analysis. NMR-based metabolomics requires relativelysimple sample preparation and provides structural information on metabolites.Our analysis and data requisition resulted in a total of 4501 metabolitesdetected. The spectra featured visually identifiable differences inthe signal ranges of 6.5–7.5, 3.5–4.0, and 2.0–2.5ppm, suggesting metabolic differences between IC patients and controls(Figure 1).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Seoul National University , Seoul 151-724, Korea.

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.

Show MeSH
Related in: MedlinePlus