Proteomics Analysis of Plasma for Early Diagnosis of Endometriosis
Abstract
OBJECTIVE: To test the hypothesis that differential surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein or peptide expression in plasma can be used in infertile women with or without pelvic pain to predict the presence of laparoscopically and histologically confirmed endometriosis, especially in the subpopulation with a normal preoperative gynecologic ultrasound examination. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis was performed on 254 plasma samples obtained from 89 women without endometriosis and 165 women with endometriosis (histologically confirmed) undergoing laparoscopies for infertility with or without pelvic pain. Data were analyzed using least squares support vector machines and were divided randomly (100 times) into a training data set (70%) and a test data set (30%). RESULTS: Minimal-to-mild endometriosis was best predicted (sensitivity 75%, 95% confidence interval [CI] 63-89; specificity 86%, 95% CI 71-94; positive predictive value 83.6%, negative predictive value 78.3%) using a model based on five peptide and protein peaks (range 4.898-14.698 m/z) in menstrual phase samples. Moderate-to-severe endometriosis was best predicted (sensitivity 98%, 95% CI 84-100; specificity 81%, 95% CI 67-92; positive predictive value 74.4%, negative predictive value 98.6%) using a model based on five other peptide and protein peaks (range 2.189-7.457 m/z) in luteal phase samples. The peak with the highest intensity (2.189 m/z) was identified as a fibrinogen β-chain peptide. Ultrasonography-negative endometriosis was best predicted (sensitivity 88%, 95% CI 73-100; specificity 84%, 95% CI 71-96) using a model based on five peptide peaks (range 2.058-42.065 m/z) in menstrual phase samples. CONCLUSION: A noninvasive test using proteomic analysis of plasma samples obtained during the menstrual phase enabled the diagnosis of endometriosis undetectable by ultrasonography with high sensitivity and specificity. LEVEL OF EVIDENCE: II.
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A combination of 5 peptide peaks discovered by SELDI-TOF mass spectrometry detected endometriosis with sensitivity of 88% and specificity of 84% in the menstrual phase.
“A combination of 5 peptide peaks, discovered by surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry, detected endometriosis with a sensitivity of 88% and a specificity of 84% in the menstrual phase [91].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [91]
Peptide fingerprinting using proteomic analysis of plasma may have utility as a noninvasive or semi-invasive diagnostic for endometriosis.
“Peptide fingerprinting using proteomic analysis of plasma may also have utility as a noninvasive or semi-invasive diagnostic for endometriosis.20”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [20]
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Cites
Anderson, N. L., & Anderson, N. G. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r200007-mcp200 · Cited by 4,414 · see citing works
Revised American Society for Reproductive Medicine classification of endometriosis: 1996
American Society for Reproductive Medicine (1997) · Fertility and Sterility · doi:10.1016/s0015-0282(97)81391-x · Cited by 3,018 · see citing works
ESHRE guideline for the diagnosis and treatment of endometriosis
Kennedy, S., Bergqvist, A., Chapron, C., D’Hooghe, T., Dunselman, G., Greb, R., Hummelshoj, L., Prentice, A., & Saridogan, E. (2005) · Human Reproduction · doi:10.1093/humrep/dei135 · Cited by 1,584 · see citing works
Self-citationXu, Q., & Liang, Y. (2001) · Chemometrics and Intelligent Laboratory Systems · doi:10.1016/s0169-7439(00)00122-2 · Cited by 1,047 · see citing works
Noyes, R. W., Hertig, A. T., & Rock, J. (1975) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(16)33500-1 · Cited by 941 · see citing works
Characterization of the Low Molecular Weight Human Serum Proteome
Tirumalai, R. S., Chan, K. C., Prieto, D. A., Issaq, H. J., Conrads, T. P., & Veenstra, T. D. (2003) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m300031-mcp200 · Cited by 846 · see citing works
The Structure and Biological Features of Fibrinogen and Fibrin
Mosesson, M. W., Siebenlist, K. R., & Meh, D. A. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb03491.x · Cited by 629 · see citing works
Optimal control by least squares support vector machines
Suykens, J. A. K., Vandewalle, J. P. L., & Moor, B. D. (2001) · Neural Networks · doi:10.1016/s0893-6080(00)00077-0 · Cited by 541 · see citing works
Delay in the diagnosis of endometriosis: a survey of women from the USA and the UK
Hadfield, R., Mardon, H., Barlow, D., & Kennedy, S. (1996) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a019270 · Cited by 517 · see citing works
Evaluating the Replicability of Significance Tests for Comparing Learning Algorithms
Bouckaert, R., & Frank, E. (2004) · Lecture notes in computer science · doi:10.1007/978-3-540-24775-3_3 · Cited by 437 · see citing works
Peripheral biomarkers of endometriosis: a systematic review
May, K. E., Conduit-Hulbert, S. A., Villar, J., Kirtley, S., Kennedy, S. H., & Becker, C. M. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmq009 · Cited by 418 · see citing works
Diagnostic delay in women with pain and endometriosis
Husby, G. K., Haugen, R. S., & Moen, M. H. (2003) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1034/j.1600-0412.2003.00168.x · Cited by 298 · see citing works
The Human Plasma Proteome: History, Character, and Diagnostic Prospects
Anderson, N. L., & Anderson, N. G. (2003) · Molecular & Cellular Proteomics · doi:10.1074/mcp.a300001-mcp200 · Cited by 286 · see citing works
A systematic review of the accuracy of ultrasound in the diagnosis of endometriosis
Moore, J. A., Copley, S. J., Morris, J., Lindsell, D. R., Golding, S. J., & Kennedy, S. (2002) · Ultrasound in Obstetrics and Gynecology · doi:10.1046/j.1469-0705.2002.00862.x · Cited by 244 · see citing works
Endometriosis, retrograde menstruation and peritoneal inflammation in women and in baboons
D'Hooghe, T. M. (2002) · Human Reproduction Update · doi:10.1093/humupd/8.1.84 · Cited by 231 · see citing works
Self-citationOpportunities and limitations of SELDI-TOF-MS in biomedical research: practical advices
Poon, T. C. W. (2007) · Expert Review of Proteomics · doi:10.1586/14789450.4.1.51 · Cited by 149 · see citing works
Jilma, B., Dirnberger, E., Löscher, I., Rumplmayr, A., Hildebrandt, J., Eichler, H.-G., Kapiotis, S., & Wagner, O. F. (1997) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(97)90060-3 · Cited by 117 · see citing works
Relationship between leptin and oestrogens in healthy women
Mannucci, E., Ognibene, A., Becorpi, A., Cremasco, F., Pellegrini, S., Ottanelli, S., Rizzello, S., Massi, G., Messeri, G., & Rotella, C. M. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1390198 · Cited by 96 · see citing works
Why We Need a Noninvasive Diagnostic Test for Minimal to Mild Endometriosis with a High Sensitivity
D’Hooghe, T. M., Mihalyi, A., Simsa, P., Kyama, C. M., Peeraer, K., Loecker, P. D., Meeuwis, L., Segal, L., & Meuleman, C. (2006) · Gynecologic and Obstetric Investigation · doi:10.1159/000093120 · Cited by 61 · see citing works
Self-citationSeeber, B., Sammel, M. D., Fan, X., Gerton, G. L., Shaunik, A., Chittams, J. L., & Barnhart, K. T. (2009) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.12.121 · Cited by 59 · see citing works
The Role of βγ and αγ Complexes in the Assembly of Human Fibrinogen
Huang, S., Cao, Z., Chung, D. W., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27942 · Cited by 54 · see citing works
Wang, L., Zheng, W., Mu, L., & Zhang, S. (2008) · International Journal of Gynecology & Obstetrics · doi:10.1016/j.ijgo.2008.01.018 · Cited by 47 · see citing works
Liu, H., Lang, J., Zhou, Q., Shan, D., & Li, Q. (2007) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.08.095 · Cited by 43 · see citing works
Wölfler, M. M., Schwamborn, K., Otten, D., Hornung, D., Liu, H., & Rath, W. H. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.03.064 · Cited by 35 · see citing works
Jing, J., Qiao, Y., Suginami, H., Taniguchi, F., Shi, H., & Wang, X. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.08.078 · Cited by 34 · see citing works
Wang, L., Zheng, W., Ding, X.-Y., Yu, J.-K., Jiang, W.-Z., & Zhang, S.-Z. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2009.08.061 · Cited by 30 · see citing works
Zhang, H., Feng, J., Chang, X., Li, Z., Wu, X., & Cui, H. (2009) · Chinese Medical Journal · doi:10.3760/cma.j.issn.0366-6999.2009.04.003 · Cited by 26 · see citing works
Ding, X., Wang, L., Ren, Y., & Zheng, W. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.04.054 · Cited by 24 · see citing works
Wang, L., Zheng, W., Yu, J., Jiang, W., Mu, L., & Zhang, S. (2007) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.01.055 · Cited by 22 · see citing works
Removal of Albumin from Multiple Human Serum Samples
Kalpana, R., de Smet, M. D., & Wiggert, B. N. (1996) · BioTechniques · doi:10.2144/96201bm05 · Cited by 21 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [13]13. triosis using artificial neural networks and protein fingerprinting. Fertil Steril 2010;93:2460-2.
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Update on biomarkers for the detection of endometriosis
Fassbender, A., Burney, R. O., F. O, D., D’Hooghe, T., & Giudice, L. (2015) · BioMed Research International · doi:10.1155/2015/130854 · Cited by 195 · see citing works
Self-citationMolecular classification of endometriosis and disease stage using high-dimensional genomic data
Tamaresis, J. S., Irwin, J. C., Goldfien, G. A., Rabban, J. T., Burney, R. O., Nezhat, C., DePaolo, L. V., & Giudice, L. C. (2014) · Endocrinology · doi:10.1210/en.2014-1490 · Cited by 168 · see citing works
Rogers, P. A. W., D’Hooghe, T. M., Fazleabas, A., Giudice, L. C., Montgomery, G. W., Petraglia, F., & Taylor, R. N. (2013) · Reproductive Sciences · doi:10.1177/1933719113477495 · Cited by 154 · see citing works
Self-citationGuidelines for the design, analysis and interpretation of ‘omics’ data: focus on human endometrium
Altmäe, S., Esteban, F. J., Stavreus-Evers, A., Simón, C., Giudice, L., Lessey, B. A., Horcajadas, J. A., Macklon, N. S., D'Hooghe, T., Campoy, C., et al. (2014) · Human Reproduction Update · doi:10.1093/humupd/dmt048 · Cited by 151 · see citing works
Self-citationFassbender, A., Vodolazkaia, A., Saunders, P., Lebovic, D., Waelkens, E., De Moor, B., & D'Hooghe, T. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.01.097 · Cited by 150 · see citing works
Self-citationEutopic endometrium in women with endometriosis: ground zero for the study of implantation defects
Lessey, B., Lebovic, D., & Taylor, R. (2013) · Seminars in Reproductive Medicine · doi:10.1055/s-0032-1333476 · Cited by 113 · see citing works
Fassbender, A., Verbeeck, N., Börnigen, D., Kyama, C. M., Bokor, A., Vodolazkaia, A., Peeraer, K., Tomassetti, C., Meuleman, C., Gevaert, O., et al. (2012) · Human Reproduction · doi:10.1093/humrep/des127 · Cited by 87 · see citing works
Self-citationNoninvasive biomarkers of endometriosis: myth or reality?
Lanišnik Rižner, T. (2014) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2014.899905 · Cited by 52 · see citing works
Serum Biomarker for Diagnosis of Endometriosis
Signorile, P. G., & Baldi, A. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24620 · Cited by 35 · see citing works
Nezhat, C. R., Oskotsky, T. T., Robinson, J. F., Fisher, S. J., Tsuei, A., Liu, B., Irwin, J. C., Gaudilliere, B., Sirota, M., Stevenson, D. K., et al. (2025) · npj Women s Health · doi:10.1038/s44294-024-00052-w · Cited by 25 · see citing works
- Authors
- Fassbender, A., Waelkens, E., Verbeeck, N., Kyama, C. M., Bokor, A., Vodolazkaia, A., Van de Plas, R., Meuleman, C., Peeraer, K., Tomassetti, C., Gevaert, O., Ojeda, F., De Moor, B., & DʼHooghe, T.
- Affiliations
- Fund for Scientific Research (BE)
- Semmelweis University (HU)
- ORCID
- Venue
- Obstetrics & Gynecology
- Published
- 2012-02
- Volume
- 119
- Issue
- 2, Part 1
- Pages
- 276-285
- ISSN
- 0029-7844 (ISSN-L)
- OpenAlex
- W2158537745
- Cited by
- 51
- References
- 30
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 7 · 2013: 12 · 2012: 2
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- endometriosis, plasma proteomics, early diagnosis, infertility, pelvic pain, menstrual cycle phases, luteal phase, non-invasive biomarkers, least squares support vector machine, diagnostic accuracy
- MeSH terms
- Adult, Blood Proteins, Endometriosis, Female, Humans, Menstruation, Predictive Value of Tests, Severity of Illness Index, Ultrasonography, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Proteomics, Young Adult
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