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基于 UPLC/QTOF/MS 平台的上皮性卵巢癌诊断代谢生物标志物的鉴定。

Identification of metabolic biomarkers to diagnose epithelial ovarian cancer using a UPLC/QTOF/MS platform.

机构信息

Department of Epidemiology and Biostatistics, Harbin Medical University, China.

出版信息

Acta Oncol. 2012 Apr;51(4):473-9. doi: 10.3109/0284186X.2011.648338. Epub 2012 Jan 27.

DOI:10.3109/0284186X.2011.648338
PMID:22283470
Abstract

BACKGROUND

Currently available tests are insufficient to distinguish patients with epithelial ovarian cancer (EOC) from normal individuals. Metabolomics, a study of metabolic processes in biologic systems, has emerged as a key technology in the measurements of small molecular metabolites in tissues or biofluids.

MATERIAL AND METHODS

To investigate the application of metabolomics on selecting EOC-associated biomarkers, 173 plasma specimens (80 newly diagnosed EOC patients and 93 normal individuals) were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/QTOF/MS). A two-step strategy was performed to select EOC-associated biomarkers. The first step was to select potential biomarkers in distinguishing 42 cancer patients from 58 normal controls through partial least-squares discriminant analysis (PLS-DA) and database searching, and the second step was to validate the discrimination performance of these biomarkers in a dataset contained 38 EOCs and 35 controls.

RESULTS

Eight candidate biomarkers were selected. The combination of these biomarkers resulted in the area of receiver operating characteristic curve (AUC) of 0.941, a sensitivity of 0.921, and a specificity of 0.886 at the best cut-off point for detecting EOC.

DISCUSSION

Our findings suggested that sharp differences in metabolic profiles exist between EOC patients and normal controls. The identified eight metabolites associated with EOC may be served as novel biomarkers for diagnosis.

摘要

背景

目前可用的检测方法不足以区分卵巢上皮癌 (EOC) 患者和正常个体。代谢组学是研究生物系统代谢过程的一种关键技术,已成为组织或生物流体中小分子代谢物测量的关键技术。

材料和方法

为了研究代谢组学在选择与 EOC 相关的生物标志物中的应用,我们使用超高效液相色谱-四极杆飞行时间质谱联用仪 (UPLC/QTOF/MS) 分析了 173 份血浆标本(80 名新诊断的 EOC 患者和 93 名正常个体)。采用两步策略来选择与 EOC 相关的生物标志物。第一步是通过偏最小二乘判别分析 (PLS-DA) 和数据库搜索来选择区分 42 名癌症患者和 58 名正常对照的潜在生物标志物,第二步是验证这些生物标志物在包含 38 名 EOC 患者和 35 名对照的数据集的判别性能。

结果

选择了 8 个候选生物标志物。这些生物标志物的组合在最佳截断点检测 EOC 时的曲线下面积 (AUC) 为 0.941,灵敏度为 0.921,特异性为 0.886。

讨论

我们的研究结果表明,EOC 患者和正常对照之间的代谢谱存在明显差异。与 EOC 相关的 8 种代谢物可能作为诊断的新型生物标志物。

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