BERKELEY, CA (UroToday.com) - We recently published data in the Journal of Proteome Research that suggests that two potential non-invasive biomarkers for interstitial cystitis have been identified using NMR-based global metabolomics analysis of urine.
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This study was conducted by our research team at Cedars-Sinai Medical Center, Los Angeles, and Seoul National University (South Korea), and found that the metabolites tyramine and 2-oxoglutarate were possibly able to discriminate 45 interstitial cystitis patients from 19 age- and gender-matched controls, thus setting the stage for prospective clinical trials of these potential biomarkers.
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. Principal component analysis and orthogonal projections to latent structure-discrimination analysis initially suggested that urine metabolites from interstitial cystitis (IC) patients and controls were clearly separated. Our team identified 140 NMR peaks with urinary levels that differed significantly between the two groups. Fifteen NMR peaks were identified as having the strongest contribution to IC signature; correlation scores were strong.
Three of the peaks were annotated as the pain-related neuromodulator tyramine, and two were 2-oxoglutarate, suggesting that levels of these two metabolites might be significantly upregulated in IC urine specimens.
Interstitial cystitis, or painful bladder syndrome, is characterized by variable symptoms such as pelvic and/or perineal pain, discomfort, urinary frequency, and urinary urgency. A poor understanding of the mechanism of IC and the lack of convenient biomarkers have posed challenges with respect to improving diagnosis and therapy for patients with IC. It is notable that only one drug is approved for the treatment of IC, and it is associated with significant side effects, including hair loss.
Our analysis uncovered other findings worth noting. The findings of the current study provide new insights into the mechanisms of the disease, and elucidate clinically relevant disease indicators that could be important in the development to next-generation treatments for IC. Future longitudinal analyses may further elucidate the impact of IC diagnosis and treatment, in particular, in the aging population.
This study was supported by grants from the National Institutes of Health, an ICA Pilot grant, the Fishbein Family IC Research Foundation/Interstitial Cystitis Association, the New York Academy of Medicine, and Children’s Hospital Boston Faculty Development. Dr. Kim is an American Urological Association Foundation Research Scholar and an Eleanor and Miles Shore Scholar of Harvard Medical School.
- Wen H, Lee T, You S, Park SH, Song H, Eilber K, Anger JT, Freeman MR, Park S*, Kim J, Urinary Metabolite Profiling Combined with Computational Analysis Predicts Interstitial Cystitis-Associated Candidate Biomarkers. Journal of Proteome Research, *co-corresponding authors (in press)
- Fiehn O, Kim J*. Metabolomics insights into pathophysiological mechanisms of interstitial cystitis. International Neurourology Journal, 18(3):106-14 (2014) *corresponding author
Jayoung Kim, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis Research Building 5071, Los Angeles, CA 90048 USA