Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages
Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages
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子宫内膜代谢组学分析揭示了诊断轻度至轻度阶段子宫内膜异位症的潜在生物标志物
DOI：
10.1016/j.fertnstert.2018.07.1104
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发表时间：
2018
影响因子：
6.7
通讯作者：
X. Liang
中科院分区：
文献类型：
--
作者：
J. Li;X. Liang
背景子宫内膜异位症的非侵入性诊断方法的敏感性和特异性，特别是在早期阶段，并不是最佳的。临床诊断指标癌抗原125（CA125）在诊断微小子宫内膜异位症方面表现较差，敏感性为24%。因此，迫切需要探索新的诊断生物标志物。我们通过超高效液相色谱联合电喷雾电离高分辨率质谱 (UHPLC-ESI-HRMS) 评估了极轻微轻度子宫内膜异位症患者和健康女性在位子宫内膜的代谢组学差异。 方法我们的研究包括 29 名经腹腔镜确诊的 I-II 期子宫内膜异位症患者和 37 名于 2014 年 1 月至 2014 年 1 月期间接受诊断性腹腔镜联合宫腔镜检查的不孕女性。 2015.通过pipelle子宫内膜活检采集在位子宫内膜样本。通过 UHPLC-ESI-HRMS 对代谢物进行定量。然后通过进行向后消除的逐步逻辑回归分析来选择生物标志物的最佳组合。结果十二种代谢物被鉴定为子宫内膜异位症相关生物标志物。子宫内膜异位症患者的在位子宫内膜代谢组学特征是次黄嘌呤、L-精氨酸、L-酪氨酸、亮氨酸、赖氨酸、肌苷、omega-3花生四烯酸、鸟苷、黄苷、溶血磷脂酰乙醇胺和天冬酰胺的浓度显着增加。相反，尿酸浓度降低。通过后向消除的逐步逻辑回归过滤代谢物，并构建包含尿酸、次黄嘌呤和溶血磷脂酰乙醇胺的模型。接受者操作特征（ROC）分析证实了这些参数对诊断轻微/轻度子宫内膜异位症的预后价值，敏感性为66.7%，特异性为90.0%。结论基于UHPLC-ESI-HRMS的代谢组学有效地表征了子宫内膜异位症在位子宫内膜的代谢组学分析。我们的研究支持嘌呤和氨基酸代谢物在子宫内膜异位症病理生理学中的重要性，并为早期子宫内膜异位症的半侵入性诊断提供潜在的生物标志物。
BackgroundThe sensitivity and specificity of non-invasive diagnostic methods for endometriosis, especially at early stages, are not optimal. The clinical diagnostic indicator cancer antigen 125 (CA125) performs poorly in the diagnosis of minimal endometriosis, with a sensitivity of 24%. Therefore, it is urgent to explore novel diagnostic biomarkers. We evaluated the metabolomic profile variation of the eutopic endometrium between minimal-mild endometriosis patients and healthy women by ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS).MethodsOur study comprised 29 patients with laparoscopically confirmed endometriosis at stages I-II and 37 infertile women who underwent diagnostic laparoscopy combined with hysteroscopy from January 2014 to January 2015. Eutopic endometrium samples were collected by pipelle endometrial biopsy. The metabolites were quantified by UHPLC-ESI-HRMS. The best combination of biomarkers was then selected by performing step-wise logistic regression analysis with backward elimination.ResultsTwelve metabolites were identified as endometriosis-associated biomarkers. The eutopic endometrium metabolomic profile of the endometriosis patients was characterized by a significant increase in the concentration of hypoxanthine, L-arginine, L-tyrosine, leucine, lysine, inosine, omega-3 arachidonic acid, guanosine, xanthosine, lysophosphatidylethanolamine and asparagine. In contrast, the concentration of uric acid was decreased. Metabolites were filtered by step-wise logistic regression with backward elimination, and a model containing uric acid, hypoxanthine, and lysophosphatidylethanolamine was constructed. Receiver-operating characteristic (ROC) analysis confirmed the prognostic value of these parameters for the diagnosis of minimal/mild endometriosis with a sensitivity of 66.7% and a specificity of 90.0%.ConclusionsMetabolomics analysis of the eutopic endometrium in endometriosis was effectively characterized by UHPLC-ESI-HRMS-based metabolomics. Our study supports the importance of purine and amino acid metabolites in the pathophysiology of endometriosis and provides potential biomarkers for semi-invasive diagnosis of early-stage endometriosis.