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：
10.1186/s12958-018-0360-z
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发表时间：
2018-04-30
期刊：
影响因子：
--
通讯作者：
Bi H
中科院分区：
文献类型：
--
作者：
Li J;Guan L;Zhang H;Gao Y;Sun J;Gong X;Li D;Chen P;Liang X;Huang M;Bi H
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并不理想，尤其是在早期阶段。临床诊断指标癌抗原125 （CA125）在诊断轻度子宫内膜异位症方面表现不佳，敏感性为24%。因此，迫切需要探索新的诊断生物标志物。我们采用超高效液相色谱-电喷雾电离高分辨率质谱联用（UHPLC-ESI-HRMS）技术评估了轻度子宫内膜异位症患者与健康女性异位子宫内膜代谢组学特征的差异。方法本研究纳入2014年1月至2015年1月29例经腹腔镜确诊的I-II期子宫内膜异位症患者和37例经诊断性腹腔镜联合宫腔镜检查的不孕症患者。异位子宫内膜标本采用管道子宫内膜活检法采集。代谢产物采用UHPLC-ESI-HRMS定量。然后通过逐步逻辑回归分析选择最佳生物标志物组合。结果12种代谢物被鉴定为子宫内膜异位症相关的生物标志物。子宫内膜异位症患者异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、黄嘌呤、溶血磷脂酰乙醇胺和天冬酰胺浓度显著升高。相反，尿酸浓度降低。代谢物采用逐步logistic回归后向消除过滤，构建了含尿酸、次黄嘌呤和溶血磷脂酰乙醇胺的模型。受试者工作特征（ROC）分析证实了这些参数对诊断轻度/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的代谢组学分析可有效表征子宫内膜异位症异位子宫内膜的代谢组学特征。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了潜在的生物标志物。
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.
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DOI：
10.4081/ejh.2015.2570
发表时间：
2015-12-09
期刊：
European journal of histochemistry : EJH
影响因子：
--
作者：
Goteri G;Altobelli E;Tossetta G;Zizzi A;Avellini C;Licini C;Lorenzi T;Castellucci M;Ciavattini A;Marzioni D
通讯作者：
Marzioni D
影响因子：
37.3
作者：
Denkert C;Budczies J;Weichert W;Wohlgemuth G;Scholz M;Kind T;Niesporek S;Noske A;Buckendahl A;Dietel M;Fiehn O
通讯作者：
Fiehn O
影响因子：
--
作者：
Marianna, Santonastaso;Alessia, Pucciarelli;Emilio, Chiosi
通讯作者：
Emilio, Chiosi
影响因子：
3.1
作者：
Bergendal, A;Naffah, S;Hillensjo, T
通讯作者：
Hillensjo, T
DOI：
10.1016/0002-9378(51)90180-9
发表时间：
1951-01-01
影响因子：
9.8
作者：
COUNSELLER, VS;CRENSHAW, JL
通讯作者：
CRENSHAW, JL