Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder, which affects 4-10 % women of reproductive age. Though accumulating scientific evidence, its pathogenesis remains unclear. In the current study, metabolic profiling as well as diagnostic biomarkers for different phenotypes of PCOS was investigated using non-invasive urinary GCMS based metabolomics. A total of 371 subjects were recruited for the study. They constituted the following groups: healthy women, those with hyperandrogenism (HA), women with insulin-resistance (IR) in PCOS. Two cross-comparisons with PCOS were performed to characterize metabolic disturbances. A total of 23 differential metabolites were found. The altered metabolic pathways included glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions, and citrate cycle and butanoate metabolism. For differential diagnosis, a panel consisting of 9 biomarkers was found from the comparison of PCOS from healthy subjects. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.8461 in the discovery phase. Predictive value of 89.17 % was found in the validation set. Besides, a panel of 8 biomarkers was discovered from PCOS with HA vs IR. The AUC for 8-biomarker panel was 0.8363, and a panel of clinical markers (homeostasis model assessment-insulin resistance and free androgen index) had 0.8327 in AUC. While these metabolites combined with clinical markers reached 0.9065 in AUC from the discovery phase, and 93.18 % in predictive value from the validation set. The result showed that differences of small-molecule metabolites in urine may reflect underlying pathogenesis of PCOS and serve as biomarkers for complementary diagnosis of the different phenotypes of PCOS.

中文翻译：

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非侵入性尿代谢组学揭示了多囊卵巢综合征及其亚型的代谢谱。

多囊卵巢综合症（PCOS）是一种异质性内分泌疾病，影响4-10％的育龄妇女。尽管积累了科学证据，但其发病机理仍不清楚。在当前的研究中，使用基于非侵入性尿液GCMS的代谢组学研究了PCOS不同表型的代谢谱以及诊断性生物标志物。总共招募了371名受试者进行研究。他们分为以下几类：健康女性，患有高雄激素血症（HA）的女性，PCOS中具有胰岛素抵抗（IR）的女性。与PCOS进行了两次交叉比较，以表征代谢紊乱。总共发现23种差异代谢物。代谢途径的改变包括乙醛酸和二羧酸的代谢，戊糖和葡萄糖醛酸酯的相互转化，柠檬酸循环和丁酸代谢。为了进行鉴别诊断，从健康受试者的PCOS比较中发现了由9种生物标志物组成的小组。在发现阶段，接收器工作特性（ROC）曲线（AUC）下的面积为0.8461。在验证集中发现预测值为89.17％。此外，从PCOS的HA与IR中发现了8种生物标记物。8-生物标志物组的AUC为0.8363，一组临床标志物（体内稳态模型评估-胰岛素抵抗和游离雄激素指数）的AUC为0.8327。从发现阶段开始，这些代谢物与临床标志物的结合使用AUC达到0.9065，而从验证组获得的预测价值为93.18％。