Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers
Abstract
BACKGROUND: Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. The aim of this study was to evaluate the combined performance of six potential plasma biomarkers in the diagnosis of endometriosis. METHODS: This case-control study was conducted in 294 infertile women, consisting of 93 women with a normal pelvis and 201 women with endometriosis. We measured plasma concentrations of interleukin (IL)-6, IL-8, tumour necrosis factor-alpha, high-sensitivity C-reactive protein (hsCRP), and cancer antigens CA-125 and CA-19-9. Analyses were done using the Kruskal-Wallis test, Mann-Whitney test, receiver operator characteristic, stepwise logistic regression and least squares support vector machines (LSSVM). RESULTS: Plasma levels of IL-6, IL-8 and CA-125 were increased in all women with endometriosis and in those with minimal-mild endometriosis, compared with controls. In women with moderate-severe endometriosis, plasma levels of IL-6, IL-8 and CA-125, but also of hsCRP, were significantly higher than in controls. Using stepwise logistic regression, moderate-severe endometriosis was diagnosed with a sensitivity of 100% (specificity 84%) and minimal-mild endometriosis was detected with a sensitivity of 87% (specificity 71%) during the secretory phase. Using LSSVM analysis, minimal-mild endometriosis was diagnosed with a sensitivity of 94% (specificity 61%) during the secretory phase and with a sensitivity of 92% (specificity 63%) during the menstrual phase. CONCLUSIONS: Advanced statistical analysis of a panel of six selected plasma biomarkers on samples obtained during the secretory phase or during menstruation allows the diagnosis of both minimal-mild and moderate-severe endometriosis with high sensitivity and clinically acceptable specificity.
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Mihalyi et al. showed the possibility of diagnosing minimal to mild endometriosis with a combination of cytokines (IL-6, IL-8, TNF a, CA 125, CA-19-9, and high-sensitivity C-reactive protein) with 60%-71% specificity and 87%-92% sensitivity.
“Mihalyi et al. showed the possibility of diagnosing minimal to mild endometriosis with the use of a combination of cytokines (interleukin [IL] 6, IL-8, tumor necrosis factor [TNF] a, cancer antigen [CA] 125, CA-19-9, and high-sensitivity C-reactive protein) with 60%-71% specificity and 87%-92% sensitivity (114).”
From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [114]
CA-125 combined with IL-8 and TNF-α in the secretory phase had sensitivity of 89.7% and specificity of 71.1%.
“CA-125 combined with interleukin-8 (IL-8) and tumor necrosis factors-α (TNF-α) in the secretory phase had a sensitivity of 89.7% and specificity of 71.1% in a study performed by Mihalyi and coworkers [36].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [36]
A panel of luteal plasma levels of IL-8, TNF-α, and CA-125 distinguished 201 women with endometriosis from 93 controls with a normal pelvis with sensitivity of 89.7% and specificity of 71.1%.
“A study by Mihalyi et al. found a panel consisting of luteal plasma levels of IL-8, TNF-α, and CA-125 that was able to distinguish between 201 women with endometriosis and 93 controls with a normal pelvis with a sensitivity of 89.7% and a specificity of 71.1% [36].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [36]
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- Authors
- Mihalyi, A., Gevaert, O., Kyama, C. M., Simsa, P., Pochet, N., De Smet, F., De Moor, B., Meuleman, C., Billen, J., Blanckaert, N., Vodolazkaia, A., Fulop, V., & D'Hooghe, T. M.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- KU Leuven (BE)
- Vlaams Instituut voor Biotechnologie (BE)
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12-09
- Volume
- 25
- Issue
- 3
- Pages
- 654-664
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2143886331
- Cited by
- 161
- References
- 38
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 4 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 6 · 2018: 6 · 2017: 8 · 2016: 14 · 2015: 14 · 2014: 13 · 2013: 17 · 2012: 12
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- KU Leuven
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Keywords
- endometriosis, non-invasive diagnosis, plasma biomarkers, interleukin-6, interleukin-8, TNF-α, high-sensitivity C-reactive protein, CA125, CA19-9, infertility, luteal phase, menstrual cycle phases, least squares support vector machine, diagnostic accuracy
- MeSH terms
- C-Reactive Protein, Endometriosis, Female, Humans, Tumor Necrosis Factor-alpha, Biomarkers, Interleukin-6, Logistic Models, Case-Control Studies, Interleukin-8, CA-125 Antigen, CA-19-9 Antigen
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