Department of Medical Research, China Medical University Hospital, Taichung, Taiwan ; China Medical University, Taichung, Taiwan.
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan ; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
PLoS One. 2013 Dec 19;8(12):e81701. doi: 10.1371/journal.pone.0081701. eCollection 2013.
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.
尿核苷与多种类型的癌症有关。在这项研究中,选择了六种靶向尿核苷,即腺苷、胞苷、3-甲基胞苷、1-甲基腺苷、肌苷和 2-脱氧鸟苷,来评估它们作为四种不同类型癌症(肺癌、胃癌、结肠癌和乳腺癌)生物标志物的作用。使用固相萃取(SPE)对尿液样本进行纯化,然后使用高效液相色谱-串联质谱法(HPLC-MS/MS)进行分析。采用曼-惠特尼 U 检验和主成分分析(PCA)比较四种不同类型癌症患者和健康对照者之间尿核苷的差异。单个核苷对不同类型癌症的诊断灵敏度范围为 14%至 69%。相比之下,一组六种核苷的诊断灵敏度范围为 37%至 69%。与单个核苷相比,与一组六种尿核苷相关的假阳性识别率低于 2%。此外,将这组六种尿核苷与癌胚抗原联合使用可提高结肠癌的诊断灵敏度。总之,研究表明,一组六种靶向核苷是乳腺癌和结肠癌的良好诊断标志物,但不是肺癌和胃癌的良好诊断标志物。