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Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis
Open accessAbstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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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“In a study comprising patients with ovarian endometriosis (n = 40), eight metabolites and 81 metabolite ratios were significantly higher in the endometriosis group compared with healthy controls undergoing laparoscopy for sterilization (n = 52) [93].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [93]
In the citing paper
“The combination of hydroxysphingomyelin C16:1 and the ratio between phosphatidylcholine C36:2 to ether-phospholipid C34:2, adjusted for the effect of age and BMI, provided a sensitivity of 90.0% and a specificity of 84.3% for the detection of endometriosis [93].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [93]
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Blood biomarkers for the non-invasive diagnosis of endometriosis
Nisenblat, V., Bossuyt, P. M., Shaikh, R., Farquhar, C. M., Jordan, V., Scheffers, C. S., Mol, B. W., JOHNSON, N. P., & Hull, M. L. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012179 · Cited by 401
Metabolomics for clinical use and research in chronic kidney disease
Hocher, B., & Adamski, J. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.30 · Cited by 339
Self-citationMetabolomics for Biomarker Discovery: Moving to the Clinic
Zhang, A., Sun, H. J., Yan, G., Wang, P., & Wang, X. (2015) · BioMed Research International · doi:10.1155/2015/354671 · Cited by 293
Kuhn, T. E., Floegel, A., Sookthai, D., Johnson, T., Rolle-Kampczyk, U. E., Otto, W., von Bergen�, M., Boeing, H., & Kaaks, R. (2016) · BMC Medicine · doi:10.1186/s12916-016-0552-3 · Cited by 247
Biomarkers for the Noninvasive Diagnosis of Endometriosis: State of the Art and Future Perspectives
Anastasiu, C. V., Moga, M., Neculau, A. E., Bălan, A., Scârneciu, I., Dragomir, R. M., Dull, A.-M., & Chicea, L.-M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051750 · Cited by 202
Metadata
- Authors
- Vouk, K., Hevir, N., Ribič-Pucelj, M., Haarpaintner, G., Scherb, H., Osredkar, J., Möller, G., Prehn, C., Rižner, T. L., & Adamski, J.
- Affiliations
- University of Ljubljana (SI)
- Ljubljana University Medical Centre (SI)
- Helmholtz Munich (DE)
- Corresponding author
- Rižner, T. Lanišnik
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-08-01
- Volume
- 27
- Issue
- 10
- Pages
- 2955-2965
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2129793603
- Cited by
- 143
- References
- 42
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 12 · 2023: 8 · 2022: 10 · 2021: 16 · 2020: 8 · 2019: 7 · 2018: 11 · 2017: 18 · 2016: 9 · 2015: 15 · 2014: 6 · 2013: 2
- FWCI
- 8.57
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Repository of the University of Ljubljana (University of Ljubljana) (publishedVersion, other-oa)
- Site cant be reached (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- endometrioma, phosphatidylcholine, sphingomyelin, plasma lipid biomarkers, targeted metabolomics, non-invasive diagnosis, glycerophospholipids, sphingolipids, acylcarnitines, apoptosis, phospholipase A2
- MeSH terms
- Adult, Age Factors, Endometriosis, Female, Humans, Phosphatidylcholines, Sensitivity and Specificity, Sphingomyelins, Biomarkers, Body Mass Index, Likelihood Functions, Logistic Models, Case-Control Studies
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