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

Abstract

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.