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Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis.
Hum. Reprod. 27, 2955-2965 (2012)
BACKGROUNDCurrent 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.METHODSIn 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.RESULTSEight 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.CONCLUSIONSOur 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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
sphingomyeline; phosphatidylcholine; ether phospholipid; acylcarnitine; ovarian endometriosis; Platelet-Activating-Factor; Human Metabolome; Expression; Apoptosis; Women; Cells; Diglycerides; Neutrophils; Choline; Profile
Language
english
Publication Year
2012
HGF-reported in Year
2012
ISSN (print) / ISBN
0268-1161
e-ISSN
1460-2350
Journal
Human Reproduction
Quellenangaben
Volume: 27,
Issue: 10,
Pages: 2955-2965
Publisher
Oxford University Press
Reviewing status
Peer reviewed
Institute(s)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Biomathematics and Biometry (IBB)
Institute of Biomathematics and Biometry (IBB)
POF-Topic(s)
30201 - Metabolic Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-505600-001
G-503800-001
G-503800-001
PubMed ID
22859507
WOS ID
WOS:000308885200011
Scopus ID
84866402322
Erfassungsdatum
2012-08-22