A metabonomic approach identifies human urinary phenylacetylglutamine as a novel marker of interstitial cystitis

Fukui, Yousuke; Katô, Masao; Inoue, Yohji; Matsubara, Akio; Itoh, Kohji

doi:10.1016/j.jchromb.2009.09.025

“…Previous studies have suggested a series of IC biomarker candidates, including antiproliferative factor13, phenylacetylglutamine14, interleukin-6, histamines15, nerve growth factor et al . Our laboratory also found tyramine and 2-oxoglutarate as urinary biomarkers for IC diagnosis16.…”

Section: Discussionmentioning

confidence: 99%

Interstitial Cystitis-Associated Urinary Metabolites Identified by Mass-Spectrometry Based Metabolomics Analysis

Kind

¹

,

Cho

²

,

Park³

et al. 2016

Sci Rep

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This study on interstitial cystitis (IC) aims to identify a unique urine metabolomic profile associated with IC, which can be defined as an unpleasant sensation including pain and discomfort related to the urinary bladder, without infection or other identifiable causes. Although the burden of IC on the American public is immense in both human and financial terms, there is no clear diagnostic test for IC, but rather it is a disease of exclusion. Very little is known about the clinically useful urinary biomarkers of IC, which are desperately needed. Untargeted comprehensive metabolomic profiling was performed using gas-chromatography/mass-spectrometry to compare urine specimens of IC patients or health donors. The study profiled 200 known and 290 unknown metabolites. The majority of the thirty significantly changed metabolites before false discovery rate correction were unknown compounds. Partial least square discriminant analysis clearly separated IC patients from controls. The high number of unknown compounds hinders useful biological interpretation of such predictive models. Given that urine analyses have great potential to be adapted in clinical practice, research has to be focused on the identification of unknown compounds to uncover important clues about underlying disease mechanisms.

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“…Previous studies have suggested a series of IC biomarker candidates, including antiproliferative factor 13 , phenylacetylglutamine 14 , interleukin-6, histamines 15 , nerve growth factor et al Our laboratory also found tyramine and 2-oxoglutarate as urinary biomarkers for IC diagnosis 16 . More recently, the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network identified Etio-S (etiocholan-3α -ol-17 -one sulfate) to discriminate IC patients from healthy controls 17 .…”

Section: Discussionmentioning

confidence: 72%

<strong>Interstitial Cystitis-Associated Urinary Metabolites </strong><strong>Identified by Mass-Spectrometry Based Metabolomics Analysis</strong>

Kim

¹

2016

Proceedings of the 1st International Electronic Conference on Metabolomics

0

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This study on interstitial cystitis (IC) aims to identify a unique urine metabolomic profile associated with IC, which can be defined as an unpleasant sensation including pain and discomfort related to the urinary bladder, without infection or other identifiable causes. Although the burden of IC on the American public is immense in both human and financial terms, there is no clear diagnostic test for IC, but rather it is a disease of exclusion. Very little is known about the clinically useful urinary biomarkers of IC, which are desperately needed. Untargeted comprehensive metabolomic profiling was performed using gas-chromatography/mass-spectrometry to compare urine specimens of IC patients or health donors. The study profiled 200 known and 290 unknown metabolites. The majority of the thirty significantly changed metabolites before false discovery rate correction were unknown compounds. Partial least square discriminant analysis clearly separated IC patients from controls. The high number of unknown compounds hinders useful biological interpretation of such predictive models. Given that urine analyses have great potential to be adapted in clinical practice, research has to be focused on the identification of unknown compounds to uncover important clues about underlying disease mechanisms.More than 3-8 million women and 1-4 million men are diagnosed with Interstitial Cystitis (IC), also known as Painful Bladder Syndrome, in the US annually 1 . IC impacts health-related qualities of life immensely, and in some instances can be more debilitating than end-stage renal disease 2,3 . In spite of an increase in the number of diagnosed cases, objective diagnostic criteria are not consistently applied in general practice 4 . Some lower urinary tract symptoms, such as overactive bladder (OAB), have symptoms in common with IC, further complicating the diagnosis. Diagnosis of the disease has been dependent on clinical parameters (e.g. pain, urgency, and frequency) due to the lack of proper conventional markers (e.g. PSA for prostate cancer diagnosis) 3,5 . Diagnostic tests include urinalysis, urine culture, cystoscopy, bladder biopsy and hydrodistention of the bladder. Nonetheless, we still lack definite criteria for the disease. Estimates of the prevalence and natural history of IC still fluctuate widely because of different diagnostic standards, populations evaluated, and challenges inherent in following patients over time 6 . Thus, the identification of sensitive and non-invasive biomarkers has the potential to greatly improve the accuracy of an IC diagnosis. However, our current understanding of mechanisms involving pelvic pain is also unclear and fragmented.Urinary metabolites represent a signature of a subject's metabolic state and may convey critical information about the pathophysiology of disease. This may be especially true for pelvic disorders because urine is the body fluid most proximal to the urinary tract. Because metabolites vary in size, chemistry and physicochemical properties, a single platform has only a ...

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“…92 One recent study using an ultra-performance liquid chromatography-mass spectrometry-based metabonomic approach showed that the urinary phebylacetylglutamine/creatinine ratio was significantly elevated in BPS/IC patients compared with controls and patients with bacterial cystitis. 93 Other elevated urinary proteins, such as hepatocarcinoma-intestine-pancrease/ pancreatitis-associated protein, 94 lower urinary levels of uromodulin and two kininogens, 95 and the beta-catenin network, 96 might also serve as potential biomarkers for the diagnosis of BPS/IC. Gene expression analysis of urine sediment found that patients with Hunner's lesions had increased pro-inflammatory gene expression similar to a prior microarray study of bladder biopsy.…”

Section: Gene Expression Analysis In Bps/icmentioning

confidence: 99%

Potential urine and serum biomarkers for patients with bladder pain syndrome/interstitial cystitis

Kuo

¹

2014

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Abbreviations & Acronyms APF = antiproliferative factor BPS/IC = bladder pain syndrome/interstitial cystitis BUC = bladder urothelial cells CRP = C-reactive protein EGF = epidermal growth factor GP51 = glycoprotein 51 HB-EGF = heparin binding growth factor-like growth factor IC = interstitial cystitis IL = interleukin MCP-1 = monocyte chemotactic protein-1 MIP-1β = macrophage inflammatory protein OAB = overactive bladder NGF = nerve growth factor NIDDK = National Institute of Diabetes, Digestive, and Kidney Diseases TNF-α = tumor necrosis factor-α ZO-1 = zonula occludens-1 Abstract: There is a lack of consensus on the pathophysiology of bladder pain syndrome/ interstitial cystitis. The chronic pain symptoms of bladder pain syndrome/interstitial cystitis refractory to local treatment could be a result of central nervous system sensitization and persisting abnormalities in the bladder wall, which activate the afferent sensory system. Evidence also shows that bladder pain syndrome/interstitial cystitis is a heterogeneous syndrome and that the two subtypes, the ulcerative (classic) and non-ulcerative types, represent different disease entities. There is a need for non-invasive markers for the differential diagnoses of the subtypes of bladder pain syndrome/interstitial cystitis, and between bladder pain syndrome/interstitial cystitis and bladder sensory disorders, such as hypersensitive bladder syndrome or overactive bladder. Bladder pain syndrome/interstitial cystitis, but not overactive bladder, involves an aberrant differentiation program in the bladder urothelium that leads to altered synthesis of several proteoglycans, cell adhesion and tight junction proteins, and bacterial defense molecules. These findings have led to the rationale for identifying urinary biomarkers to detect bladder pain syndrome/interstitial cystitis in patients with frequency urgency syndrome. Recently, the markers that have been the focus of the most research are antiproliferative factor, epidermal growth factor, heparin-binding epidermal growth factor, glycosaminoglycans and bladder nitric oxide. In addition, inflammatory proteins in the urine and serum play important roles in the pathogenesis of bladder pain syndrome/interstitial cystitis. The urinary proteome is an easily accessible source of biomarkers for differentiation between inflammatory bladder disorders. Analysis of multiple urinary proteins and serum cytokines could provide a diagnostic basis for bladder pain syndrome/interstitial cystitis, and could be a tool for the differential diagnosis of bladder pain syndrome/interstitial cystitis and other sensory bladder disorders.

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A metabonomic approach identifies human urinary phenylacetylglutamine as a novel marker of interstitial cystitis

Cited by 37 publications

References 20 publications

Interstitial Cystitis-Associated Urinary Metabolites Identified by Mass-Spectrometry Based Metabolomics Analysis

Interstitial Cystitis-Associated Urinary Metabolites Identified by Mass-Spectrometry Based Metabolomics Analysis

<strong>Interstitial Cystitis-Associated Urinary Metabolites </strong><strong>Identified by Mass-Spectrometry Based Metabolomics Analysis</strong>

Potential urine and serum biomarkers for patients with bladder pain syndrome/interstitial cystitis

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