Urinary Nucleosides as Biomarkers of Breast, Colon, Lung, and Gastric Cancer in Taiwanese

Urinary nucleosides are associated with many types of cancer. In this study, six targeted urinary nucleosides, namely adenosine, cytidine, 3-methylcytidine, 1-methyladenosine, inosine, and 2-deoxyguanosine, were chosen to evaluate their role as biomarkers of four different types of cancer: lung cancer, gastric cancer, colon cancer, and breast cancer. Urine samples were purified using solid-phase extraction (SPE) and then analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The Mann-Whitney U test and Principal Component Analysis (PCA) were used to compare differences in urinary nucleosides between patients with one of four types of cancer and healthy controls. The diagnostic sensitivity of single nucleosides for different types of cancer ranged from 14% to 69%. In contrast, the diagnostic sensitivity of a set of six nucleosides ranged from 37% to 69%. The false-positive identification rate associated with the set of six nucleosides in urine was less than 2% compared with that of less than 5% for a single nucleoside. Furthermore, combining the set of six urinary nucleosides with carcinoembryonic antigen improved the diagnostic sensitivity for colon cancer. In summary, the study show that a set of six targeted nucleosides is a good diagnostic marker for breast and colon cancers but not for lung and gastric cancers.

[1]  Michał Jan Markuszewski,et al.  Liquid chromatography tandem mass spectrometry study of urinary nucleosides as potential cancer markers. , 2013, Journal of chromatography. A.

[2]  R. Carabias-Martínez,et al.  Development and validation of a hydrophilic interaction chromatography-tandem mass spectrometry method with on-line polar extraction for the analysis of urinary nucleosides. Potential application in clinical diagnosis. , 2011, Journal of chromatography. A.

[3]  R. Kaliszan,et al.  The state-of-the-art determination of urinary nucleosides using chromatographic techniques “hyphenated” with advanced bioinformatic methods , 2011, Analytical and bioanalytical chemistry.

[4]  Roman Kaliszan,et al.  Altered levels of nucleoside metabolite profiles in urogenital tract cancer measured by capillary electrophoresis. , 2010, Journal of pharmaceutical and biomedical analysis.

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

[6]  A. Jukkola-Vuorinen,et al.  8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer , 2010, British Journal of Cancer.

[7]  Hong-min Liu,et al.  Separation and identification of purine nucleosides in the urine of patients with malignant cancer by reverse phase liquid chromatography/electrospray tandem mass spectrometry. , 2009, Journal of mass spectrometry : JMS.

[8]  L. Jeng,et al.  Analysis of urinary nucleosides as potential tumor markers in human colorectal cancer by high performance liquid chromatography/electrospray ionization tandem mass spectrometry. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[9]  B. Chung,et al.  Evaluation of urinary nucleosides in breast cancer patients before and after tumor removal. , 2009, Clinical biochemistry.

[10]  Han Min Woo,et al.  Mass spectrometry based metabolomic approaches in urinary biomarker study of women's cancers. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[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]  K. Kuo,et al.  Classification of lung cancer patients and controls by chromatography of modified nucleosides in serum. , 1989, Cancer research.

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

[14]  S. Belman,et al.  High turnover rate of transfer RNA in tumor tissue. , 1977, Cancer research.

[15]  K. Kuo,et al.  High-performance liquid chromatographic separation and quantitation of nucleosides in urine and some other biological fluids. , 1977, Clinical chemistry.

[16]  C. Heierli,et al.  [Serum creatinine determination without protein precipitation]. , 1972, Clinica chimica acta; international journal of clinical chemistry.

[17]  E. Borek Transfer RNA and transfer RNA modification in differentiation and neoplasia. Introduction. , 1971, Cancer research.

[18]  L. Jeng,et al.  Analysis of urinary nucleosides as potential tumor markers in human breast cancer by high performance liquid chromatography/electrospray ionization tandem mass spectrometry. , 2011, Clinica chimica acta; international journal of clinical chemistry.

[19]  C. G. Baker Transfer RNA and transfer RNA modification in differentiation and neoplasia. Introductory remarks. , 1971, Cancer research.