Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
J Pharm Biomed Anal. 2010 Dec 15;53(5):1305-12. doi: 10.1016/j.jpba.2010.07.031. Epub 2010 Aug 4.
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.
核苷的代谢谱在尿水平上的研究与机体的病理生理状态密切相关。细胞核中 RNA(主要是 tRNA)的转录后修饰负责恶性疾病期间核苷水平的变化。在本文中,收集了 160 名泌尿生殖道癌患者和 96 名健康对照者的 256 种代谢物谱,由 19 种核苷组成,并应用了这种方法进行了研究。该方法包括尿液提取物的分析以及通过先进的统计数据分析工具(如主成分分析(PCA)、层次聚类分析(HCA)、K-最近邻法(kNN)和具有概率函数的偏最小二乘判别分析(p-PLS-DA))来研究收集的核苷和修饰核苷谱。结果表明,癌症疾病中代谢物谱的改变主要表现为大多数核苷尿液水平的倍数变化。此外,与健康对照组相比,观察到的代谢物与代谢物之间的比值在泌尿生殖道癌症患者中有所不同。评估了尿核苷谱与癌症疾病存在之间的关系。癌症患者和非癌症健康受试者的区分具有 76.5%的敏感性和 80.2%的特异性。所得到的结果证明了代谢组学方法在研究具有高度诊断潜力的泌尿生殖道癌症疾病中尿核苷谱的有用性。尿核苷谱可作为泌尿生殖道癌症疾病诊断的可靠且方便的工具。