CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
J Proteome Res. 2011 May 6;10(5):2625-32. doi: 10.1021/pr200173q. Epub 2011 Apr 19.
The aim of this study was to use a two steps strategy metabolomics to screen/identify and validate novel metabolic biomarker(s) for epithelial ovarian cancer (EOC). In the screening step, serum samples from 27 healthy women, 28 benign ovarian tumors, and 29 EOCs were analyzed by using LC-MS based nontargeted metabolomics. The three groups were separated with OSC filtered PLS-DA model, and six metabolites (27-nor-5β-cholestane-3,7,12,24,25 pentol glucuronide (CPG), phenylalanine, glycocholic acid, propionylcarnitine, Phe-Phe and Lyso PC (18:2)) were considered as potential biomarker candidates. In the validation step, the six metabolites were analyzed in targeted metabolomics by LC-selective ion monitoring mass spectrometry in another 685 serum samples with various clinical backgrounds. As a result, CPG was evaluated to be a potential biomarker and its content was elevated in EOC tissues compared with benign ovarian tumor tissues (p = 0.0005). Besides, CPG levels were found to be up-regulated in early stage EOC and in the three types of EOC histological types. Other variables such as nonovarian diseases, medicine consumption, gynecological inflammations, and menopausal state did not interfere in using CPG as diagnosis marker. CPG was found to be complementary to CA125. Our findings suggest that CPG can be considered a statistical relevant biomarker of EOC, ready for early stage detection.
本研究旨在采用两步策略代谢组学筛选/鉴定和验证上皮性卵巢癌（EOC）的新型代谢生物标志物。在筛选步骤中，采用基于 LC-MS 的非靶向代谢组学分析了 27 名健康女性、28 名良性卵巢肿瘤和 29 名 EOC 患者的血清样本。使用 OSC 过滤的 PLS-DA 模型将三组分离，认为六种代谢物（27-降-5β-胆甾烷-3,7,12,24,25 五醇葡萄糖醛酸（CPG）、苯丙氨酸、甘胆酸、丙酰肉碱、Phe-Phe 和 Lyso PC（18:2））为潜在的生物标志物候选物。在验证步骤中，通过 LC-选择离子监测质谱法在具有不同临床背景的另 685 份血清样本中进行了靶向代谢组学分析。结果表明，CPG 被评估为一种潜在的生物标志物，其在 EOC 组织中的含量高于良性卵巢肿瘤组织（p=0.0005）。此外，在早期 EOC 和三种 EOC 组织学类型中，CPG 水平升高。其他变量，如非卵巢疾病、药物使用、妇科炎症和绝经状态，不影响使用 CPG 作为诊断标志物。CPG 与 CA125 具有互补性。我们的研究结果表明，CPG 可被视为 EOC 的统计相关生物标志物，可用于早期检测。
