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A comprehensive urinary metabolomic approach for identifying kidney cancer

A comprehensive urinary metabolomic approach for identifying kidney cancer,10.1016/j.ab.2007.01.028,Analytical Biochemistry,Tobias Kind,Vladimir Tolst

A comprehensive urinary metabolomic approach for identifying kidney cancer   (Citations: 69)
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The diagnosis of cancer by examination of the urine has the potential to improve patient outcomes by means of earlier detection. Due to the fact that the urine contains metabolic signatures of many biochemical pathways, this biofluid is ideally suited for metabolomic analysis, especially involving diseases of the kidney and urinary system. In this pilot study, we test three independent analytical techniques for suitability for detection of renal cell carcinoma (RCC) in urine of affected patients. Hydrophilic interaction chromatography (HILIC–LC–MS), reversed-phase ultra performance liquid chromatography (RP–UPLC–MS), and gas chromatography time-of-flight mass spectrometry (GC–TOF–MS) all were used as complementary separation techniques. The combination of these techniques is best suited to cover a very large part of the urine metabolome by enabling the detection of both lipophilic and hydrophilic metabolites present therein. In this study, it is demonstrated that sample pretreatment with urease dramatically alters the metabolome composition apart from removal of urea. Two new freely available peak alignment methods, MZmine and XCMS, are used for peak detection and retention time alignment. The results are analyzed by a feature selection algorithm with subsequent univariate analysis of variance (ANOVA) and a multivariate partial least squares (PLS) approach. From more than 2000 mass spectral features detected in the urine, we identify several significant components that lead to discrimination between RCC patients and controls despite the relatively small sample size. A feature selection process condensed the significant features to less than 30 components in each of the data sets. In future work, these potential biomarkers will be further validated with a larger patient cohort. Such investigation will likely lead to clinically applicable assays for earlier diagnosis of RCC, as well as other malignancies, and thereby improved patient prognosis.
Journal: Analytical Biochemistry - ANAL BIOCHEM , vol. 363, no. 2, pp. 185-195, 2007
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    • ...Serum metabolomics has been applied to other clinical populations with cancer with a view to developing novel early diagnostic biomarkers in renal cancer (Kind et al. 2007; Kim et al. 2009), colorectal cancer (Ritchie et al. 2010), pancreatic cancer (Urayama et al. 2010), leukaemia (MacIntyre et al. 2010), ovarian cancer (Guan et al. 2009; Odunsi et al. 2005) and oral cancer (Tiziani et al. 2009)...

    Mamas Mamaset al. The role of metabolites and metabolomics in clinically applicable biom...

    • ..., 95:5 methyl/phenyl and 50:50 methyl/phenyl...

    David Broadhurstet al. Procedures for large-scale metabolic profiling of serum and plasma usi...

    • ...High resolution mass analysers such as time of flight (TOF) (Kind et al. 2007), Fourier transform ion cyclotron resonance (Sleighter and Hatcher 2007) and the recently introduced LTQ-Orbitrap analysers (Dunn et al. 2008) then remains the instruments of choice in this field...
    • ...The first metabolomics studies were originally and primarily focused on clinical (Kind et al. 2007; Lewis et al. 2008) or pharmaceutical applications (Robertson 2005) but new more specific areas of application have recently emerged, for instance in the anti-doping field...

    Fanny KiekenGaudet al. Generation and processing of urinary and plasmatic metabolomic fingerp...

    • ...For example, metabolomic analysis has been used for biomarker development for the detection of different kinds of human cancers including bladder [12, 13, 14], kidney [15, 16], epithelial ovarian [17], breast [18], pancreatic [19], lung [20], gastric [21], esophageal [22], colorectal [23, 24], cervical [25], and cancer cells [26]...
    • ...For example, urine samples for MS analysis have been analyzed neat [12], centrifuged, and diluted [16], passed through solid phase extraction columns [29], treated and incubated with various reagents [30], and extracted with different solvents [31, 32]...

    Que N. Vanet al. Metabolic Profiling for the Detection of Bladder Cancer

    • ...Urine-based metabolomics has been applied in the researches of early detection and renal toxicity [6, 9], diagnosis, biomarker identification, and pathogenic pathway of kidney cancer [8, 16]...

    Xianfu Gaoet al. Parallel metabolomics of urine and serum revealed systematic alteratio...

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