Altered levels of nucleoside metabolite profiles in urogenital tract cancer measured by capillary electrophoresis.

Metabolic profiles of nucleosides studied on the level of urine are closely related to the pathophysiological status of the organism. Posttranscriptional modifications of RNA (mostly tRNA) in cell nucleus are responsible for change of nucleoside levels during malignant disease. In this paper, 256 metabolite profiles from 160 urogenital tract cancer patients and 96 healthy controls, composed of 19 nucleosides were collected and studied with the application of such an approach. This approach comprised of the analysis of urine extracts and the investigation of collected nucleoside and modified nucleoside profiles by advanced statistical data processing tools such as principal component analysis (PCA), hierarchical cluster analysis (HCA), K-Nearest Neighbor method (kNN) and partial least squares-discriminant analysis with probabilistic function (p-PLS-DA). It has been shown that alterations of metabolite profiles in cancer diseases are mainly expressed by the fold change of the urine levels of most nucleosides. In addition, observed metabolite-to-metabolite ratios differ in urogenital cancer patients compared to healthy controls. The obtained relationships between urinary nucleoside profiles and the presence of cancer diseases have been evaluated. Discrimination of the cancer patients and the non-cancer healthy subjects is with 76.5% sensitivity and 80.2% specificity. The presented results prove the usefulness of the metabolomic approach in studying urinary nucleoside profiles with high diagnostic potency in urogenital cancer diseases. Profiles of urinary nucleosides might be employed as a reliable and convenient tool in the diagnostics of urogenital tract cancer diseases.

[1]  S. Hansen,et al.  Separation of nucleosides using capillary electrochromatography. , 1999, Journal of chromatography. A.

[2]  Beata Walczak,et al.  Identifying potential biomarkers in LC‐MS data , 2007 .

[3]  R. Kaliszan,et al.  Development and validation of urinary nucleosides and creatinine assay by capillary electrophoresis with solid phase extraction. , 2007, Journal of pharmaceutical and biomedical analysis.

[4]  H. Özen,et al.  Urinary markers for urothelial cancer , 2003, BJU international.

[5]  E. Schiffer Biomarkers for prostate cancer , 2007, World Journal of Urology.

[6]  Hongwei Kong,et al.  Determination of urinary nucleosides by direct injection and coupled-column high-performance liquid chromatography. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[7]  Shen Lv,et al.  Clinical significance and prognostic value of urinary nucleosides in breast cancer patients. , 2005, Clinical biochemistry.

[8]  R. Lehmann,et al.  Capillary electrophoresis of urinary normal and modified nucleosides of cancer patients. , 1998, Journal of chromatography. A.

[9]  Ying Zhang,et al.  HMDB: the Human Metabolome Database , 2007, Nucleic Acids Res..

[10]  Qing Yang,et al.  Diagnosis of liver cancer using HPLC-based metabonomics avoiding false-positive result from hepatitis and hepatocirrhosis diseases. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[11]  O. Herbarth,et al.  Modified nucleosides: an accurate tumour marker for clinical diagnosis of cancer, early detection and therapy control , 2006, British Journal of Cancer.

[12]  B. Walczak,et al.  Discrimination of biofilm samples using pattern recognition techniques , 2007, Analytical and bioanalytical chemistry.

[13]  D L Massart,et al.  Boosting partial least squares. , 2005, Analytical chemistry.

[14]  H. Liebich,et al.  Capillary electrophoretic profiling and pattern recognition analysis of urinary nucleosides from uterine myoma and cervical cancer patients. , 2001, Journal of chromatography. B, Biomedical sciences and applications.

[15]  K. Itoh,et al.  Urinary pseudouridine in patients with lymphoma: comparison with other clinical parameters. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[16]  B. Melichar,et al.  Neopterin in renal cell carcinoma: inhalational administration of interleukin-2 is not accompanied by a rise of urinary neopterin. , 2005, Luminescence : the journal of biological and chemical luminescence.

[17]  B. Chung,et al.  Analysis of polyamines as carbamoyl derivatives in urine and serum by liquid chromatography-tandem mass spectrometry. , 2008, Biomedical chromatography : BMC.

[18]  Ya Xiong Zhang,et al.  Artificial neural networks based on principal component analysis input selection for clinical pattern recognition analysis. , 2007, Talanta.

[19]  Yinfa Ma,et al.  Recent developments in the determination of urinary cancer biomarkers by capillary electrophoresis , 2004, Electrophoresis.

[20]  Oliver Fiehn,et al.  A comprehensive urinary metabolomic approach for identifying kidney cancerr. , 2007, Analytical biochemistry.

[21]  R. Lewensohn,et al.  Metabolomics: Moving to the Clinic , 2010, Journal of Neuroimmune Pharmacology.

[22]  R. Kaliszan,et al.  Metabolomic approach for determination of urinary nucleosides as potential tumor markers using electromigration techniques , 2010, Electrophoresis.

[23]  S. Eckhardt,et al.  Clinical Applications of Metabolomics in Oncology: A Review , 2009, Clinical Cancer Research.

[24]  R Kaliszan,et al.  Increasing conclusiveness of metabonomic studies by chem-informatic preprocessing of capillary electrophoretic data on urinary nucleoside profiles. , 2007, Journal of pharmaceutical and biomedical analysis.

[25]  Ronald D. Snee,et al.  Validation of Regression Models: Methods and Examples , 1977 .

[26]  K. Kuo,et al.  Quantitative high-performance liquid chromatography of nucleosides in biological materials. , 1978, Journal of chromatography.

[27]  G. Kong,et al.  Direct determination of nucleosides in the urine of patients with breast cancer using column-switching liquid chromatography-tandem mass spectrometry. , 2006, Biomedical chromatography : BMC.

[28]  Russ Greiner,et al.  Investigations of the effects of gender, diurnal variation, and age in human urinary metabolomic profiles. , 2007, Analytical chemistry.

[29]  L. A. Stone,et al.  Computer Aided Design of Experiments , 1969 .

[30]  Laura K Schnackenberg,et al.  Global metabolic profiling and its role in systems biology to advance personalized medicine in the 21st Century , 2007, Expert review of molecular diagnostics.