Abstract
The purpose of this study was to use metabonomic profiling to identify a potential specific biomarker pattern in urine as a noninvasive bladder cancer (BC) detection strategy. A liquid chromatography-mass spectrometry based method, which utilized both reversed phase liquid chromatography and hydrophilic interaction chromatography separations, was performed, followed by multivariate data analysis to discriminate the global urine profiles of 27 BC patients and 32 healthy controls. Data from both columns were combined, and this combination proved to be effective and reliable for partial least squares-discriminant analysis. Following a critical selection criterion, several metabolites showing significant differences in expression levels were detected. Receiver operating characteristic analysis was used for the evaluation of potential biomarkers. Carnitine C9:1 and component I, were combined as a biomarker pattern, with a sensitivity and specificity up to 92.6% and 96.9%, respectively, for all patients and 90.5% and 96.9%, respectively for low-grade BC patients. Metabolic pathways of component I and carnitine C9:1 are discussed. These results indicate that metabonomics is a practicable tool for BC diagnosis given its high efficacy and economization. The combined biomarker pattern showed better performance than single metabolite in discriminating bladder cancer patients, especially low-grade BC patients, from healthy controls.
Highlights
Bladder cancer (BC)1 is one of the most commonly occurring tumors in the urinary system
We found that urinary acylcarnitine deficiency was prevalent in BC patients
Acylcarnitines are generated when corresponding fatty acids are activated into acyl-coenzyme A and participate in a carnitine palmitoyl transferase I (CPT I)-catalyzed reaction
Summary
Bladder cancer (BC) is one of the most commonly occurring tumors in the urinary system. A series of important proteomic biomarkers have been reported in recent years, including telomerase, hyaluronidase, CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), nuclear matrix protein 22, cystatin B, cytokeratins, growth factors, and surviving [1, 6, 7] All these urinary markers present challenges for obtaining both high specificity and high sensitivity at the same time [6]. Cellular tumor genes linked to molecular pathway alterations produce or secrete specific metabolites into biofluids [9] These metabolites can potentially serve as biomarkers for cancer diagnosis [10]. Issaq et al reported that metabonomics using RPLC-MS had the potential to be a noninvasive early detection strategy for BC [17] They did not further investigate the biomarkers related to bladder tumorigenesis
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