Frickenschmidt Antje, Frohlich Holger, Bullinger Dino, Zell Andreas, Laufer Stefan, Gleiter Christoph H, Liebich Hartmut, Kammerer Bernd
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University Hospital Tubingen, Tubingen, Germany.
Biomarkers. 2008 Jun;13(4):435-49. doi: 10.1080/13547500802012858.
Modified nucleosides are formed post-transcriptionally in RNA. In cancer disease, the cell turnover and thus RNA metabolism is increased, yielding higher concentrations of excreted modified nucleosides. In the presented study, urinary ribonucleosides were used to differentiate between breast cancer patients and healthy volunteers. The nucleosides were extracted from urine samples using affinity chromatography and subsequently analyzed via liquid chromatography ion trap mass spectrometry (LC-IT-MS). The peak areas were related to the internal standard isoguanosine and to the urinary creatinine level. For bioinformatic pattern recognition we used the support vector machine. We examined 113 urine samples from breast cancer patients (stage Tis-T4) and 99 control samples from healthy volunteers. We achieved a sensitivity of 87.67% and a specificity of 89.90% when including 31 nucleosides. The medical metabonomics concept based on the urinary nucleoside profile reveals a significantly improved classification compared with currently applied breast cancer biomarkers such as CA15-3.
修饰核苷在RNA转录后形成。在癌症疾病中，细胞更新以及RNA代谢增加，导致排泄的修饰核苷浓度更高。在本研究中，尿核糖核苷被用于区分乳腺癌患者和健康志愿者。使用亲和色谱法从尿液样本中提取核苷，随后通过液相色谱离子阱质谱法（LC-IT-MS）进行分析。峰面积与内标异鸟苷以及尿肌酐水平相关。对于生物信息模式识别，我们使用了支持向量机。我们检测了113份来自乳腺癌患者（Tis-T4期）的尿液样本和99份来自健康志愿者的对照样本。当纳入31种核苷时，我们实现了87.67%的灵敏度和89.90%的特异性。基于尿核苷谱的医学代谢组学概念显示，与目前应用的乳腺癌生物标志物如CA15-3相比，分类有显著改善。
