Abstract
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.
Highlights
Davis et al [1] were the first researchers to compare the concentration and ratio of urinary nucleosides between healthy individuals and patients with cancer
The nucleosides were isolated with a boronate affinity column and separated using reversed-phase high-performance liquid chromatographic (HPLC)–ultraviolet (UV) methods
Common pretreatment methods include solid phase extraction (SPE) with phenylboronic acid (PBA) as an extraction bed or gel for purification of vicinal hydroxyl groups involved in the structure of nucleosides [3,4], cation-exchange extraction for purification of positively charged nitrogen in nucleosides and deoxynucleosides [5], and C18 extraction for purification of hydrophobic moieties in nucleosides and deoxynucleosides [6,7]
Summary
Davis et al [1] were the first researchers to compare the concentration and ratio of urinary nucleosides between healthy individuals and patients with cancer. The nucleosides were isolated with a boronate affinity column and separated using reversed-phase high-performance liquid chromatographic (HPLC)–ultraviolet (UV) methods. Sample preparation normally involves an extraction procedure to obtain well-purified and concentrated nucleosides from complex matrices in urine prior to instrumental analysis. Common pretreatment methods include solid phase extraction (SPE) with phenylboronic acid (PBA) as an extraction bed or gel for purification of vicinal hydroxyl groups involved in the structure of nucleosides [3,4], cation-exchange extraction for purification of positively charged nitrogen in nucleosides and deoxynucleosides [5], and C18 extraction for purification of hydrophobic moieties in nucleosides and deoxynucleosides [6,7]. Separation of urinary nucleosides is often carried out by chromatographic methods such as HPLC or Ultra Performance Liquid Chromatography (UPLC)
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