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Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis

子宫内膜异位症 鞘磷脂 内科学 优势比 逻辑回归 代谢物 医学 内分泌学 胃肠病学 肿瘤科 胆固醇
作者
Katja Vouk,Neli Hevir,Martina Ribič-Pucelj,G. Haarpaintner,Hagen Scherb,J. Osredkar,Gabriele Möller,Cornelia Prehn,Tea Lanišnik Rižner,Jerzy Adamski
出处
期刊:Human Reproduction [Oxford University Press]
卷期号:27 (10): 2955-2965 被引量:117
标识
DOI:10.1093/humrep/des152
摘要

Current non-invasive diagnostic methods for endometriosis lack sensitivity and specificity. In search for new diagnostic biomarkers for ovarian endometriosis, we used a hypothesis-generating targeted metabolomics approach.In a case-control study, we collected plasma of study participants and analysed their metabolic profiles. We selected a group of 40 patients with ovarian endometriosis who underwent laparoscopic surgery and a control group of 52 healthy women who underwent sterilization at the University Clinical Centre Ljubljana, Slovenia. Over 140 targeted analytes included glycerophospholipids, sphingolipids and acylcarnitines. The analytes were quantified by electrospray ionization tandem mass spectrometry. For assessing the strength of association between the metabolite or metabolite ratios and the disease, we used crude and adjusted odds ratios. A stepwise logistic regression procedure was used for selecting the best combination of biomarkers.Eight lipid metabolites were identified as endometriosis-associated biomarkers due to elevated levels in patients compared with controls. A model containing hydroxysphingomyelin SMOH C16:1 and the ratio between phosphatidylcholine PCaa C36:2 to ether-phospholipid PCae C34:2, adjusted for the effect of age and the BMI, resulted in a sensitivity of 90.0%, a specificity of 84.3% and a ratio of the positive likelihood ratio to the negative likelihood ratio of 48.3.Our results suggest that endometriosis is associated with elevated levels of sphingomyelins and phosphatidylcholines, which might contribute to the suppression of apoptosis and affect lipid-associated signalling pathways. Our findings suggest novel potential routes for therapy by specifically blocking highly up-regulated isoforms of phosphpolipase A2 and lysophosphatidylcholine acyltransferase 4.
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