State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029 Jiangsu, China.
J Pharm Biomed Anal. 2020 Jun 5;185:113262. doi: 10.1016/j.jpba.2020.113262. Epub 2020 Mar 17.
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.
多囊卵巢综合征（PCOS）是一种异质性内分泌疾病，影响着 4-10%的育龄妇女。尽管积累了大量的科学证据，但它的发病机制仍不清楚。在目前的研究中，我们使用非侵入性的尿液 GCMS 代谢组学方法研究了代谢特征谱以及不同表型 PCOS 的诊断生物标志物。共有 371 名受试者参与了这项研究。他们分为以下几组：健康女性、高雄激素血症（HA）患者、PCOS 伴胰岛素抵抗（IR）的女性。对 PCOS 进行了两次交叉比较，以表征代谢紊乱。共发现 23 个差异代谢物。改变的代谢途径包括乙醛酸和二羧酸代谢、戊糖和葡萄糖醛酸相互转化、柠檬酸循环和丁酸盐代谢。为了进行鉴别诊断，从健康受试者与 PCOS 的比较中发现了一个由 9 个生物标志物组成的小组。在发现阶段，接收器操作特性（ROC）曲线下的面积（AUC）为 0.8461。在验证集中发现了 89.17%的预测值。此外，从 PCOS 伴 HA 与 IR 的比较中发现了一个由 8 个生物标志物组成的小组。8 个生物标志物小组的 AUC 为 0.8363，而一组临床标志物（稳态模型评估-胰岛素抵抗和游离雄激素指数）的 AUC 为 0.8327。当这些代谢物与临床标志物结合时，从发现阶段的 AUC 达到 0.9065，从验证集的预测值达到 93.18%。结果表明，尿液中小分子代谢物的差异可能反映了 PCOS 的潜在发病机制，并可作为补充诊断不同表型 PCOS 的生物标志物。
