Identification and validation of novel serum markers for early diagnosis of endometriosis
Abstract
BACKGROUND: Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis. METHODS: A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation. RESULTS: The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis. CONCLUSIONS: Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Autoantibodies against different epitopes of TPM3, SLP2, and TMOD3 were significantly elevated in serum of endometriosis patients with both minimal/mild and moderate/severe disease.
“Autoantibodies against different epitopes of tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2), and tropomodulin 3 (TMOD3) were significantly elevated in the serum of endometriosis patients with both minimal/mild and moderate/severe disease [80].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [80]
Cites
PROCHECK: a program to check the stereochemical quality of protein structures
Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889892009944 · Cited by 24,581 · see citing works
Comparative Protein Modelling by Satisfaction of Spatial Restraints
Šali, A., & Blundell, T. L. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1626 · Cited by 12,977 · see citing works
Verification of protein structures: Patterns of nonbonded atomic interactions
Colovos, C., & Yeates, T. O. (1993) · Protein Science · doi:10.1002/pro.5560020916 · Cited by 4,506 · 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
A Method to Identify Protein Sequences That Fold into a Known Three-Dimensional Structure
Bowie, J. U., Lüthy, R., & Eisenberg, D. (1991) · Science · doi:10.1126/science.1853201 · Cited by 2,851 · see citing works
Prediction of continuous B‐cell epitopes in an antigen using recurrent neural network
Saha, S., & Raghava, G. P. S. (2006) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21078 · Cited by 1,758 · see citing works
A semi‐empirical method for prediction of antigenic determinants on protein antigens
Kolaskar, A. S., & Tongaonkar, P. (1990) · FEBS Letters · doi:10.1016/0014-5793(90)80535-q · Cited by 1,493 · see citing works
Improved method for predicting linear B-cell epitopes.
Larsen, J., Lund, O., & Nielsen, M. (2006) · Immunome Research · doi:10.1186/1745-7580-2-2 · Cited by 1,243 · see citing works
Comparative protein modeling by satisfaction of spatial restraints
⩽ali, A. (1995) · Molecular Medicine Today · doi:10.1016/s1357-4310(95)91170-7 · Cited by 785 · see citing works
Prediction of residues in discontinuous B‐cell epitopes using protein 3D structures
Andersen, P. H., Nielsen, M., & Lund, O. (2006) · Protein Science · doi:10.1110/ps.062405906 · Cited by 631 · see citing works
Saha, S., & Raghava, G. P. S. (2004) · Lecture notes in computer science · doi:10.1007/978-3-540-30220-9_16 · Cited by 451 · see citing works
The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis
Mol, B. W. J., Bayram, N., Lijmer, J. G., Wiegerinck, M. A. H. M., Bongers, M. Y., van der Veen, F., & Bossuyt, P. M. M. (1998) · Fertility and Sterility · doi:10.1016/s0015-0282(98)00355-0 · Cited by 355 · see citing works
Priorities for Endometriosis Research: Recommendations From an International Consensus Workshop
Rogers, P. A. W., D’Hooghe, T. M., Fazleabas, A., Gargett, C. E., Giudice, L. C., Montgomery, G. W., Rombauts, L., Salamonsen, L. A., & Zondervan, K. T. (2009) · Reproductive Sciences · doi:10.1177/1933719108330568 · Cited by 346 · see citing works
Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator
Hevér, A., Roth, R. B., Hevezi, P. A., Marin, M. E., Acosta, J. A., Acosta, H., Rojas, J., Herrera, R. M. B., Grigoriadis, D. E., White, E., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703451104 · Cited by 254 · see citing works
Patients’ report on how endometriosis affects health, work, and daily life
Fourquet, J., Gao, X., Zavala, D., Orengo, J. C., Abac, S., Ruiz, A., Laboy, J., & Flores, I. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2009.09.017 · Cited by 252 · cited 2× · see citing works
“pain, dysmenorrhoea, dyspareunia and infertility; this leads to a considerable burden in terms of healthcare costs and the quality of life (Fourquet et al., 2010; Mcleod and Retzloff, 2010).”
BackgroundNon-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers
Mihalyi, A., Gevaert, O., Kyama, C. M., Simsa, P., Pochet, N., De Smet, F., De Moor, B., Meuleman, C., Billen, J., Blanckaert, N., et al. (2010) · Human Reproduction · doi:10.1093/humrep/dep425 · Cited by 161 · see citing works
Somigliana, E. (2004) · Human Reproduction · doi:10.1093/humrep/deh312 · Cited by 138 · see citing works
Epidemiology of Endometriosis:
MCLEOD, B. S., & Retzloff, M. G. (2010) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0b013e3181db7bde · Cited by 112 · see citing works
Zhang, L., Ding, F., Cao, W., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1858 · Cited by 108 · see citing works
Fowler, P., Tattum, J., Bhattacharya, S., Klonisch, T. C., Hombach‐Klonisch, S., Gazvani, R., Lea, R. G., Miller, I. D., Simpson, W. G., & Cash, P. (2006) · PROTEOMICS · doi:10.1002/pmic.200600469 · Cited by 102 · see citing works
Zhang, H., Niu, Y., Feng, J., Guo, H., Ye, X., & Cui, H. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.01.028 · Cited by 101 · see citing works
González‐Sapienza, G., Lorenzo, C., & Nieto, A. (2000) · Journal of Clinical Microbiology · doi:10.1128/jcm.38.11.3979-3983.2000 · Cited by 96 · see citing works
Ametzazurra, A., Matorras, R., García-Velasco, J. A., Prieto, B., Simón, L., Martinez, A., & Nagore, D. (2008) · Human Reproduction · doi:10.1093/humrep/den450 · Cited by 85 · see citing works
An association of IgG anti-laminin-1 autoantibodies with endometriosis in infertile patients
Inagaki, J. (2003) · Human Reproduction · doi:10.1093/humrep/deg148 · Cited by 67 · see citing works
Socolov, R. V., Buţureanu, S., Angioni, S. L., Sindilar, A., Boiculese, L. V., Cozma, L. G., & Socolov, D. G. (2010) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2010.10.008 · Cited by 65 · see citing works
Endometrial antigens involved in the autoimmunity of endometriosis
MATHUR, S. P., Chihal, H. J., Homm, R. J., Garza, D. E., Rust, P. F., & Williamson, H. O. (1988) · Fertility and Sterility · doi:10.1016/s0015-0282(16)60362-x · Cited by 62 · see citing works
Seeber, 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
Noninvasive diagnosis of endometriosis: the role of imaging and markers
Brosens, J. J., Timmerman, D., Starzinski‐Powitz, A., & Brosens, I. A. (2003) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/s0889-8545(02)00055-4 · Cited by 54 · see citing works
Alpha tropomyosin as a self-antigen in patients with Behçet's disease
Mahesh, S. P., Li, Z., Buggage, R. R., et al. (2005) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2005.02760.x · Cited by 49 · see citing works
Multiple endometrial antigens are targeted in autoimmune endometriosis
Gajbhiye, R., Suryawanshi, A. R., Khan, S., Meherji, P. K., Warty, N. R., Raut, V., Chehna-Patel, N., & Khole, V. V. (2008) · Reproductive BioMedicine Online · doi:10.1016/s1472-6483(10)60147-2 · Cited by 48 · see citing works
Self-citationFuldeore, M., Chwalisz, K., Marx, S., Wu, N., Boulanger, L., Ma, L., & Lamothe, K. (2011) · Journal of Medical Economics · doi:10.3111/13696998.2010.549532 · Cited by 47 · see citing works
Evaluation of endometrial biomarkers for semi-invasive diagnosis of endometriosis
Kyama, C. M., Mihalyi, A., Gevaert, O., Waelkens, E., Simsa, P., de Plas, R. V., Meuleman, C., Moor, B. D., & D’Hooghe, T. M. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.06.084 · Cited by 45 · see citing works
Pregnancy Loss and Endometriosis: Pathogenic Role of Anti-Laminin-1 Autoantibodies
Inagaki, J., Kondo, A., Lopez, L. R., Shoenfeld, Y., & Matsuura, E. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1361.059 · Cited by 44 · see citing works
Dighiero, G., Lymberi, P., Monot, C., et al. (1990) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1990.tb05402.x · Cited by 44 · see citing works
Serum Antiendometrial Antibodies and Diagnosis of Endometriosis
Randall, G. W., Gantt, P. A., Poe‐Zeigler, R. L., Bergmann, C. A., Noel, M. E., Strawbridge, W. R., Richardson‐Cox, B., Hereford, J. R., & Reiff, R. H. (2007) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2007.00523.x · Cited by 44 · see citing works
Cui, Z., Zhang, L., Hua, Z., et al. (2007) · Oncology Reports · doi:10.3892/or.17.4.829 · Cited by 42 · see citing works
Autoimmunity to tropomyosin isoforms in ulcerative colitis (UC) patients and unaffected relatives
Biancone, L., Monteleone, G., Marasco, R., et al. (1998) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1998.00610.x · Cited by 42 · see citing works
Tagoma, A., Haller‐Kikkatalo, K., Utt, M., Teesalu, K., Salumets, A., & Uibo, R. (2010) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2010.00808.x · Cited by 41 · see citing works
Differential Proteomics Leads to Identification of Domain‐Specific Epididymal Sperm Proteins
Suryawanshi, A. R., Khan, S. A., Gajbhiye, R., et al. (2011) · Journal of Andrology · doi:10.2164/jandrol.110.010967 · Cited by 33 · see citing works
Self-citationIdentification of anti‐α‐enolase autoantibody as a novel serum marker for endometriosis
Nabeta, M., Abe, Y., Kagawa‐Miki, L., Haraguchi, R., Kito, K., Ueda, N., Sugita, A., Yokoyama, M., Kusanagi, Y., & Ito, M. (2009) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200900055 · Cited by 32 · see citing works
Identification of novel immunodominant epididymal sperm proteins using combinatorial approach
Khan, S. A., Suryawanshi, A. R., Ranpura, S. A., et al. (2009) · Reproduction · doi:10.1530/rep-09-0052 · Cited by 31 · see citing works
Self-citationIdentification of anti-syntaxin 5 autoantibody as a novel serum marker of endometriosis
Nabeta, M., Abe, Y., Takaoka, Y., Kusanagi, Y., & Ito, M. (2011) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2011.04.012 · Cited by 26 · see citing works
Serum anti-PDIK1L autoantibody as a novel marker for endometriosis
Nabeta, M., Abe, Y., Haraguchi, R., Kito, K., Kusanagi, Y., & Ito, M. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.03.008 · Cited by 22 · see citing works
Anti-endometrial antibodies in women measured by an enzyme-linked immunosorbent assay
Fernández-Shaw, S., Kennedy, S. H., Hicks, B. R., Edmonds, K., Starkey, P. M., & Barlow, D. H. (1996) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a019351 · Cited by 18 · see citing works
Synthetic peptides for diagnostic use
Meloen, R. H., Langedijk, J. P. M., & Langeveld, J. (1997) · Veterinary Quarterly · doi:10.1080/01652176.1997.9694755 · Cited by 15 · see citing works
Antibodies against myofibrillar proteins in myasthenia gravis patients.
Takaya, M., Kawahara, S., Namba, T., et al. (1992) · PubMed · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
“Autoantibodies against different epitopes of tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2), and tropomodulin 3 (TMOD3) were significantly elevated in the serumof endometriosis patients with bothminimal/mild and moderate/severe disease [80].”
Diagnostic accuracy of cancer antigen 125 for endometriosis: A systematic review and meta-analysis
Hirsch, M., Duffy, J., Davis, C., Nieves Plana, M., Khan, K., & on behalf of the International Collaboration to Harmonise Outcomes and Measures for Endometriosis (2016) · BJOG: An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.14055 · Cited by 156 · see citing works
Fassbender, 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
Noninvasive 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
- Authors
- Gajbhiye, R., Sonawani, A., Khan, S., Suryawanshi, A., Kadam, S., Warty, N., Raut, V., & Khole, V.
- Affiliations
- ICMR National Institute for Research on Women's Health (IN)
- Institute of Life Sciences (IN)
- Corresponding author
- Khole, V.
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-12-08
- Volume
- 27
- Issue
- 2
- Pages
- 408-417
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2165441271
- Cited by
- 53
- References
- 46
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 4 · 2013: 6
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Indian Council of Medical Research
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- endometriosis, serum biomarkers, autoantibodies, early diagnosis, non-invasive diagnosis, TPM3, STOML2, CA125, proteomics, ELISA validation, sensitivity and specificity
- MeSH terms
- Adult, Antibody Specificity, Autoantibodies, Autoantigens, Blood Proteins, Cross-Sectional Studies, Endometriosis, Female, Humans, Membrane Proteins, Peptide Fragments, Peptide Mapping, Sensitivity and Specificity, Severity of Illness Index, Tropomyosin, Cohort Studies, Biomarkers, Immunodominant Epitopes, Early Diagnosis, Tropomodulin, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review