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

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.

Statistical-Based Approach in Potential Diagnostic Application of Urinary Nucleosides in Urogenital Tract Cancer

“…Pathological verification of urogenital tract cancer was completed by biopsy or surgical resection of tumors (see details in Table 1). The Tumor-Node-Metastasis (TNM) classification (American Joint Committee on Cancer), as well as tumor grading system, were used in order to establish the stage and grade of the disease [17][18][19]. Patients were classified by disease stage into two subphenotypes: those diagnosed from T1 stage and those for whom the stage was above T1.…”

“…Seidel et al [48] reported different nucleosides' excretion pattern within the same stage of a disease, suggesting determination of more than four nucleoside profiles in order to evaluate the disease status. Likewise in [38], Hsu et al [18] postulated that studies should be limited to one particular type of disease due to the occurrence of variations in urinary nucleoside levels between breast, colon, lung and gastric cancer patients and healthy individuals. Different sets of nucleosides, significantly associated with different cancer types were identified with the exception for urinary nucleoside profile in gastric and lung cancer patients, for which the profile was similar [18].…”

“…Likewise in [38], Hsu et al [18] postulated that studies should be limited to one particular type of disease due to the occurrence of variations in urinary nucleoside levels between breast, colon, lung and gastric cancer patients and healthy individuals. Different sets of nucleosides, significantly associated with different cancer types were identified with the exception for urinary nucleoside profile in gastric and lung cancer patients, for which the profile was similar [18]. With this regard, an idea worth considering for the future studies is to analyze the concentration of nucleosides in each disease cohort separately; however, one should keep in mind that the sample size constitutes a major limitation as shown in our study.…”

“…These modifications are essential to improve integrity, biological Statistical-based approach in potential diagnostic application of urinary nucleosides in urogenital tract cancer Research Article activity and efficiency of RNA in different biochemical processes. Thus, any disease or metabolic imbalance affecting RNA turnover or breakdown will have an impact on the levels of excreted nucleosides [17,18]. A number of papers have emphasized that nucleoside profiles may be used as a novel diagnostic tool in various cancers [19][20][21].…”

Analysis of urinary nucleosides as potential cancer markers determined using LC–MS technique

“…The most popular analytical column is C18 [6,[15][16][17][18][19][57][58][59], however HILIC columns are becoming more popular due to the polar character of compounds like nucleosides [55,60]. Besides, there is also a trend to resemble conditions like UHPLC using routine HPLC system in order to reduce eddy-diffusion and increase flow rates with controlled back pressures.…”