{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:43:48Z","timestamp":1793447028941,"version":"4.5.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["J3-1755"],"award-info":[{"award-number":["J3-1755"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endometriosis is a common non-malignant gynecological disease that significantly compromises fertility and quality of life of the majority of patients. The gold standard for diagnosis is visual inspection of the pelvic organs by surgical laparoscopy and there are no biomarkers that would allow non-invasive diagnosis. The pathogenesis of endometriosis is not completely understood, thus analysis of peritoneal fluid might contribute in this respect. Our prospective case\u2013control study included 58 patients undergoing laparoscopy due to infertility, 32 patients with peritoneal endometriosis (cases) and 26 patients with unexplained primary infertility (controls). Discovery proteomics using antibody microarrays that covered 1360 proteins identified 16 proteins with different levels in cases<jats:italic>versus<\/jats:italic>the control patients. The validation using an ELISA approach confirmed significant differences in the levels of cartilage oligomeric matrix protein (COMP) and transforming growth factor-\u03b2-induced protein ig-h3 (TGFBI) and nonsignificant differences in angiotensinogen (AGT). A classification model based on a linear support vector machine revealed AUC of\u2009&gt;\u20090.83, sensitivity of 0.81 and specificity of 1.00. Differentially expressed proteins represent candidates for diagnostic and prognostic biomarkers or drug targets. Our findings have brought new knowledge that will be helpful in the understanding of the pathophysiology of endometriosis and warrant further studies in blood samples.<\/jats:p>","DOI":"10.1038\/s41598-021-00299-2","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T10:09:32Z","timestamp":1634897372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Proteomic analysis of peritoneal fluid identified COMP and TGFBI as new candidate biomarkers for endometriosis"],"prefix":"10.1038","volume":"11","author":[{"given":"V.","family":"Jan\u0161a","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Klan\u010di\u010d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Pu\u0161i\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Vrta\u010dnik Bokal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Ban Frange\u017e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Lani\u0161nik","family":"Ri\u017ener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"issue":"5","key":"299_CR1","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1177\/1933719113477495","volume":"20","author":"PA Rogers","year":"2013","unstructured":"Rogers, P. A. et al. Defining future directions for endometriosis research: Workshop report from the 2011 World Congress of Endometriosis in Montpellier, France. Reprod. Sci. 20(5), 483\u2013499 (2013).","journal-title":"Reprod. Sci."},{"issue":"4","key":"299_CR2","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/S0002-9378(15)30003-X","volume":"14","author":"JA Sampson","year":"1927","unstructured":"Sampson, J. A. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am. J. Obstet. Gynecol. 14(4), 422\u2013469 (1927).","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"3","key":"299_CR3","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1093\/humrep\/det457","volume":"29","author":"GA Dunselman","year":"2014","unstructured":"Dunselman, G. A. et al. ESHRE guideline: Management of women with endometriosis. Hum. Reprod. 29(3), 400\u2013412 (2014).","journal-title":"Hum. Reprod."},{"issue":"4","key":"299_CR4","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1586\/14737159.2015.1015994","volume":"15","author":"TL Ri\u017ener","year":"2015","unstructured":"Ri\u017ener, T. L. Diagnostic potential of peritoneal fluid biomarkers of endometriosis. Expert Rev. Mol. Diagn. 15(4), 557\u2013580 (2015).","journal-title":"Expert Rev. Mol. Diagn."},{"issue":"3","key":"299_CR5","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.fertnstert.2012.06.029","volume":"98","author":"RO Burney","year":"2012","unstructured":"Burney, R. O. & Giudice, L. C. Pathogenesis and pathophysiology of endometriosis. Fertil. Steril. 98(3), 511\u2013519 (2012).","journal-title":"Fertil. Steril."},{"key":"299_CR6","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/bs.acc.2018.12.002","volume":"89","author":"LM Coutinho","year":"2019","unstructured":"Coutinho, L. M., Ferreira, M. C., Rocha, A. L. L., Carneiro, M. M. & Reis, F. M. New biomarkers in endometriosis. Adv. Clin. Chem. 89, 59\u201377 (2019).","journal-title":"Adv. Clin. Chem."},{"issue":"3","key":"299_CR7","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1159\/000093121","volume":"62","author":"A Agic","year":"2006","unstructured":"Agic, A. et al. Is endometriosis associated with systemic subclinical inflammation? Gynecol. Obstet. Investig. 62(3), 139\u2013147 (2006).","journal-title":"Gynecol. Obstet. Investig."},{"issue":"2","key":"299_CR8","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1177\/1933719116654991","volume":"24","author":"PA Rogers","year":"2017","unstructured":"Rogers, P. A. et al. Research priorities for endometriosis. Reprod. Sci. 24(2), 202\u2013226 (2017).","journal-title":"Reprod. Sci."},{"issue":"3","key":"299_CR9","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1586\/14737159.2014.899905","volume":"14","author":"TL Ri\u017ener","year":"2014","unstructured":"Ri\u017ener, T. L. Noninvasive biomarkers of endometriosis: Myth or reality? Expert Rev. Mol. Diagn. 14(3), 365\u2013385 (2014).","journal-title":"Expert Rev. Mol. Diagn."},{"key":"299_CR10","first-page":"1","volume":"90","author":"J Vid","year":"2021","unstructured":"Vid, J., Josko, O., Eda, V. B., Lani\u0161nik, T. R. & Helena, B. F. Biomarkers of endometriosis: How far have we come and where are we going? Slov. Med. J. 90, 1\u201310 (2021).","journal-title":"Slov. Med. J."},{"issue":"5","key":"299_CR11","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1093\/humupd\/4.5.741","volume":"4","author":"PR Koninckx","year":"1998","unstructured":"Koninckx, P. R., Kennedy, S. H. & Barlow, D. H. Endometriotic disease: The role of peritoneal fluid. Hum. Reprod. Update 4(5), 741\u2013751 (1998).","journal-title":"Hum. Reprod. Update"},{"issue":"5","key":"299_CR12","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1093\/humupd\/dmt024","volume":"19","author":"VJ Young","year":"2013","unstructured":"Young, V. J., Brown, J. K., Saunders, P. T. & Horne, A. W. The role of the peritoneum in the pathogenesis of endometriosis. Hum. Reprod. Update 19(5), 558\u2013569 (2013).","journal-title":"Hum. Reprod. Update"},{"issue":"4","key":"299_CR13","first-page":"333","volume":"55","author":"MA Bedaiwy","year":"2003","unstructured":"Bedaiwy, M. A. & Falcone, T. Peritoneal fluid environment in endometriosis. Clinicopathological implications. Minerva Ginecol. 55(4), 333\u2013345 (2003).","journal-title":"Minerva Ginecol."},{"issue":"6","key":"299_CR14","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1074\/mcp.M900419-MCP200","volume":"9","author":"C Schr\u00f6der","year":"2010","unstructured":"Schr\u00f6der, C. et al. Dual-color proteomic profiling of complex samples with a microarray of 810 cancer-related antibodies. Mol. Cell Proteomics 9(6), 1271\u20131280 (2010).","journal-title":"Mol. Cell Proteomics"},{"key":"299_CR15","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1186\/1471-2105-11-556","volume":"11","author":"M Sill","year":"2010","unstructured":"Sill, M., Schr\u00f6der, C., Hoheisel, J. D., Benner, A. & Zucknick, M. Assessment and optimisation of normalisation methods for dual-colour antibody microarrays. BMC Bioinform. 11, 556 (2010).","journal-title":"BMC Bioinform."},{"issue":"D1","key":"299_CR16","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk, D. et al. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 47(D1), D607\u2013D613 (2019).","journal-title":"Nucleic Acids Res."},{"issue":"5","key":"299_CR17","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/S0015-0282(97)81391-X","volume":"67","author":"American Society for Reproductive","year":"1997","unstructured":"American Society for Reproductive. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil. Steril. 67(5), 817\u2013821 (1997).","journal-title":"Fertil. Steril."},{"key":"299_CR18","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1136\/emermed-2017-206735","volume":"34","author":"ZH Hoo","year":"2017","unstructured":"Hoo, Z. H., Candlish, J. & Teare, D. What is an ROC curve? Emerg. Med. J. 34, 357\u2013359 (2017).","journal-title":"Emerg. Med. J."},{"issue":"5","key":"299_CR19","first-page":"CD012179","volume":"2016","author":"V Nisenblat","year":"2016","unstructured":"Nisenblat, V. et al. Blood biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst. Rev. 2016(5), CD012179 (2016).","journal-title":"Cochrane Database Syst. Rev."},{"issue":"5","key":"299_CR20","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.3390\/ijms21051750","volume":"21","author":"CV Anastasiu","year":"2020","unstructured":"Anastasiu, C. V. et al. Biomarkers for the noninvasive diagnosis of endometriosis: State of the art and future perspectives. Int. J. Mol. Sci. 21(5), 1750 (2020).","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"299_CR21","doi-asserted-by":"publisher","first-page":"16738","DOI":"10.1038\/s41598-019-52899-8","volume":"9","author":"T Knific","year":"2019","unstructured":"Knific, T. et al. Multiplex analysis of 40 cytokines do not allow separation between endometriosis patients and controls. Sci. Rep. 9(1), 16738 (2019).","journal-title":"Sci. Rep."},{"issue":"2","key":"299_CR22","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1007\/s43032-019-00081-w","volume":"27","author":"E Waelkens","year":"2020","unstructured":"Waelkens, E., Vanhie, A., Peterse, D., Fassbender, A. & D\u2019Hooghe, T. The use of antibody arrays in the discovery of new plasma biomarkers for endometriosis. Reprod. Sci. 27(2), 751\u2013762 (2020).","journal-title":"Reprod. Sci."},{"issue":"9","key":"299_CR23","doi-asserted-by":"publisher","first-page":"3402","DOI":"10.1021\/pr060680q","volume":"6","author":"S Ferrero","year":"2007","unstructured":"Ferrero, S. et al. Proteomic analysis of peritoneal fluid in women with endometriosis. J. Proteome Res. 6(9), 3402\u20133411 (2007).","journal-title":"J. Proteome Res."},{"key":"299_CR24","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12014-017-9142-4","volume":"14","author":"G Grande","year":"2017","unstructured":"Grande, G. et al. Cervical mucus proteome in endometriosis. Clin. Proteomics 14, 7 (2017).","journal-title":"Clin. Proteomics"},{"issue":"6","key":"299_CR25","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1016\/j.fertnstert.2013.01.133","volume":"99","author":"F Itoh","year":"2013","unstructured":"Itoh, F. et al. Possible involvement of signal transducer and activator of transcription-3 in cell-cell interactions of peritoneal macrophages and endometrial stromal cells in human endometriosis. Fertil. Steril. 99(6), 1705\u20131713 (2013).","journal-title":"Fertil. Steril."},{"issue":"1","key":"299_CR26","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1159\/000119091","volume":"66","author":"BC Jee","year":"2008","unstructured":"Jee, B. C., Suh, C. S., Kim, S. H. & Moon, S. Y. Serum soluble CD163 and interleukin-6 levels in women with ovarian endometriomas. Gynecol. Obstet. Investig. 66(1), 47\u201352 (2008).","journal-title":"Gynecol. Obstet. Investig."},{"issue":"1","key":"299_CR27","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ajog.2005.12.010","volume":"195","author":"NA Bersinger","year":"2006","unstructured":"Bersinger, N. A. et al. PAPP-A and osteoprotegerin, together with interleukin-8 and RANTES, are elevated in the peritoneal fluid of women with endometriosis. Am. J. Obstet. Gynecol. 195(1), 103\u2013108 (2006).","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"4","key":"299_CR28","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.fertnstert.2017.11.036","volume":"109","author":"J Mar\u00ed-Alexandre","year":"2018","unstructured":"Mar\u00ed-Alexandre, J. et al. Micro-RNA profile and proteins in peritoneal fluid from women with endometriosis: Their relationship with sterility. Fertil. Steril. 109(4), 675\u2013684 (2018).","journal-title":"Fertil. Steril."},{"issue":"5","key":"299_CR29","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1111\/j.1471-0528.1992.tb13756.x","volume":"99","author":"A Prentice","year":"1992","unstructured":"Prentice, A. et al. Epidermal growth factor receptor expression in normal endometrium and endometriosis: An immunohistochemical study. Br. J. Obstet. Gynaecol. 99(5), 395\u2013398 (1992).","journal-title":"Br. J. Obstet. Gynaecol."},{"issue":"7","key":"299_CR30","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1093\/molehr\/6.7.610","volume":"6","author":"S Scotti","year":"2000","unstructured":"Scotti, S., Regidor, P. A., Schindler, A. E. & Winterhager, E. Reduced proliferation and cell adhesion in endometriosis. Mol. Hum. Reprod. 6(7), 610\u2013617 (2000).","journal-title":"Mol. Hum. Reprod."},{"issue":"5","key":"299_CR31","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s00428-009-0755-5","volume":"454","author":"C Uzan","year":"2009","unstructured":"Uzan, C. et al. Status of HER1 and HER2 in peritoneal, ovarian and colorectal endometriosis and ovarian endometrioid adenocarcinoma. Virchows Arch. 454(5), 525\u2013529 (2009).","journal-title":"Virchows Arch."},{"issue":"4","key":"299_CR32","first-page":"1097","volume":"79","author":"JC Huang","year":"1994","unstructured":"Huang, J. C. & Yeh, J. Quantitative analysis of epidermal growth factor receptor gene expression in endometriosis. J. Clin. Endocrinol. Metab. 79(4), 1097\u20131101 (1994).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"299_CR33","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1111\/j.1749-6632.1991.tb37922.x","volume":"626","author":"A Bergqvist","year":"1991","unstructured":"Bergqvist, A., Borg, A. & Ljungberg, O. Protooncogenes in endometriotic and endometrial tissue. Ann. N. Y. Acad. Sci. 626, 276\u2013283 (1991).","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"2","key":"299_CR34","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1159\/000167798","volume":"67","author":"K Ejskjaer","year":"2009","unstructured":"Ejskjaer, K. et al. Expression of the epidermal growth factor system in eutopic endometrium from women with endometriosis differs from that in endometrium from healthy women. Gynecol. Obstet. Investig. 67(2), 118\u2013126 (2009).","journal-title":"Gynecol. Obstet. Investig."},{"issue":"9","key":"299_CR35","doi-asserted-by":"publisher","first-page":"6132","DOI":"10.1016\/S0021-9258(18)42671-3","volume":"267","author":"E Hedbom","year":"1992","unstructured":"Hedbom, E. et al. Cartilage matrix proteins. An acidic oligomeric protein (COMP) detected only in cartilage. J. Biol. Chem. 267(9), 6132\u20136136 (1992).","journal-title":"J. Biol. Chem."},{"issue":"5","key":"299_CR36","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/j.jhep.2016.06.003","volume":"65","author":"F Magdaleno","year":"2016","unstructured":"Magdaleno, F. et al. Cartilage oligomeric matrix protein participates in the pathogenesis of liver fibrosis. J. Hepatol. 65(5), 963\u2013971 (2016).","journal-title":"J. Hepatol."},{"issue":"8","key":"299_CR37","doi-asserted-by":"publisher","first-page":"10461","DOI":"10.3390\/ijms130810461","volume":"13","author":"MP Ween","year":"2012","unstructured":"Ween, M. P., Oehler, M. K. & Ricciardelli, C. Transforming growth factor-beta-induced protein (TGFBI)\/(\u03b2ig-H3): A matrix protein with dual functions in ovarian cancer. Int. J. Mol. Sci. 13(8), 10461\u201310477 (2012).","journal-title":"Int. J. Mol. Sci."},{"issue":"7","key":"299_CR38","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1002\/ijc.25494","volume":"128","author":"MP Ween","year":"2011","unstructured":"Ween, M. P. et al. Transforming growth factor-beta-induced protein secreted by peritoneal cells increases the metastatic potential of ovarian cancer cells. Int. J. Cancer 128(7), 1570\u20131584 (2011).","journal-title":"Int. J. Cancer"},{"issue":"3","key":"299_CR39","first-page":"344","volume":"232","author":"J Tang","year":"2007","unstructured":"Tang, J. et al. BetaIg-h3 is involved in the HAb18G\/CD147-mediated metastasis process in human hepatoma cells. Exp. Biol. Med. (Maywood) 232(3), 344\u2013352 (2007).","journal-title":"Exp. Biol. Med. (Maywood)"},{"issue":"1","key":"299_CR40","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3181\/0806-RM-187","volume":"234","author":"J Tang","year":"2009","unstructured":"Tang, J., Wu, Y. M., Zhao, P., Jiang, J. L. & Chen, Z. N. Betaig-h3 interacts with alpha3beta1 integrin to promote adhesion and migration of human hepatoma cells. Exp. Biol. Med. (Maywood) 234(1), 35\u201339 (2009).","journal-title":"Exp. Biol. Med. (Maywood)"},{"issue":"3","key":"299_CR41","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1101\/gad.1632008","volume":"22","author":"C Ma","year":"2008","unstructured":"Ma, C. et al. Extracellular matrix protein betaig-h3\/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes Dev. 22(3), 308\u2013321 (2008).","journal-title":"Genes Dev."},{"issue":"22","key":"299_CR42","doi-asserted-by":"publisher","first-page":"9112","DOI":"10.1158\/0008-5472.CAN-08-0851","volume":"68","author":"AY Khakoo","year":"2008","unstructured":"Khakoo, A. Y., Sidman, R. L., Pasqualini, R. & Arap, W. Does the renin-angiotensin system participate in regulation of human vasculogenesis and angiogenesis? Cancer Res. 68(22), 9112\u20139115 (2008).","journal-title":"Cancer Res."},{"issue":"11","key":"299_CR43","doi-asserted-by":"publisher","first-page":"585","DOI":"10.5603\/GP.a2017.0106","volume":"88","author":"LJ Kowalczy\u0144ska","year":"2017","unstructured":"Kowalczy\u0144ska, L. J. et al. Is M235T polymorphism of the angiotensinogen gene involved in the development of endometriosis? Ginekol. Pol. 88(11), 585\u2013590 (2017).","journal-title":"Ginekol. Pol."},{"issue":"4","key":"299_CR44","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1095\/biolreprod.108.073411","volume":"80","author":"JA Stilley","year":"2009","unstructured":"Stilley, J. A., Woods-Marshall, R., Sutovsky, M., Sutovsky, P. & Sharpe-Timms, K. L. Reduced fecundity in female rats with surgically induced endometriosis and in their daughters: A potential role for tissue inhibitors of metalloproteinase 1. Biol. Reprod. 80(4), 649\u2013656 (2009).","journal-title":"Biol. Reprod."},{"issue":"1","key":"299_CR45","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/S0015-0282(00)01670-8","volume":"75","author":"HW Chung","year":"2001","unstructured":"Chung, H. W. et al. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 mRNA expression in ectopic and eutopic endometrium in women with endometriosis: A rationale for endometriotic invasiveness. Fertil. Steril. 75(1), 152\u2013159 (2001).","journal-title":"Fertil. Steril."},{"issue":"4","key":"299_CR46","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1095\/biolreprod65.4.1297","volume":"65","author":"KE Cox","year":"2001","unstructured":"Cox, K. E., Piva, M. & Sharpe-Timms, K. L. Differential regulation of matrix metalloproteinase-3 gene expression in endometriotic lesions compared with endometrium. Biol. Reprod. 65(4), 1297\u20131303 (2001).","journal-title":"Biol. Reprod."},{"key":"299_CR47","doi-asserted-by":"publisher","first-page":"569","DOI":"10.2741\/1552","volume":"10","author":"HE Zhou","year":"2005","unstructured":"Zhou, H. E. & Nothnick, W. B. The relevancy of the matrix metalloproteinase system to the pathophysiology of endometriosis. Front. Biosci. 10, 569\u2013575 (2005).","journal-title":"Front. Biosci."},{"issue":"12","key":"299_CR48","first-page":"3784","volume":"80","author":"KL Sharpe-Timms","year":"1995","unstructured":"Sharpe-Timms, K. L. et al. Partial purification and amino acid sequence analysis of endometriosis protein-II (ENDO-II) reveals homology with tissue inhibitor of metalloproteinases-1 (TIMP-1). J. Clin. Endocrinol. Metab. 80(12), 3784\u20133787 (1995).","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"2","key":"299_CR49","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1055\/s-2003-41322","volume":"21","author":"KG Osteen","year":"2003","unstructured":"Osteen, K. G., Yeaman, G. R. & Bruner-Tran, K. L. Matrix metalloproteinases and endometriosis. Semin. Reprod. Med. 21(2), 155\u2013164 (2003).","journal-title":"Semin. Reprod. Med."},{"issue":"5","key":"299_CR50","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1095\/biolreprod56.5.1181","volume":"56","author":"WB Nothnick","year":"1997","unstructured":"Nothnick, W. B., Soloway, P. & Curry, T. E. Jr. Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during the periovulatory period in female mice lacking a functional TIMP-1 gene. Biol. Reprod. 56(5), 1181\u20131188 (1997).","journal-title":"Biol. Reprod."},{"issue":"5","key":"299_CR51","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1095\/biolreprod64.5.1285","volume":"64","author":"TE Curry Jr","year":"2001","unstructured":"Curry, T. E. Jr. & Osteen, K. G. Cyclic changes in the matrix metalloproteinase system in the ovary and uterus. Biol. Reprod. 64(5), 1285\u20131296 (2001).","journal-title":"Biol. Reprod."},{"issue":"2","key":"299_CR52","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1095\/biolreprod.109.083287","volume":"83","author":"JA Stilley","year":"2010","unstructured":"Stilley, J. A. et al. Neutralizing TIMP1 restores fecundity in a rat model of endometriosis and treating control rats with TIMP1 causes anomalies in ovarian function and embryo development. Biol. Reprod. 83(2), 185\u2013194 (2010).","journal-title":"Biol. Reprod."},{"issue":"8","key":"299_CR53","doi-asserted-by":"publisher","first-page":"2840","DOI":"10.3390\/ijms21082840","volume":"21","author":"A Luddi","year":"2020","unstructured":"Luddi, A. et al. Expression of matrix metalloproteinases and their inhibitors in endometrium: High levels in endometriotic lesions. Int. J. Mol Sci. 21(8), 2840 (2020).","journal-title":"Int. J. Mol Sci."},{"issue":"3","key":"299_CR54","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/S0046-8177(96)90070-2","volume":"27","author":"H Niikura","year":"1996","unstructured":"Niikura, H., Sasano, H., Kaga, K., Sato, S. & Yajima, A. Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium. Hum. Pathol. 27(3), 282\u2013289 (1996).","journal-title":"Hum. Pathol."},{"issue":"1","key":"299_CR55","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.ygyno.2006.07.015","volume":"104","author":"K Ejskjaer","year":"2007","unstructured":"Ejskjaer, K. et al. Expression of the epidermal growth factor system in endometrioid endometrial cancer. Gynecol. Oncol. 104(1), 158\u2013167 (2007).","journal-title":"Gynecol. Oncol."},{"issue":"8","key":"299_CR56","doi-asserted-by":"publisher","first-page":"2538","DOI":"10.1016\/j.fertnstert.2009.11.011","volume":"93","author":"GL Ding","year":"2010","unstructured":"Ding, G. L. et al. Attenuated oocyte fertilization and embryo development associated with altered growth factor\/signal transduction induced by endometriotic peritoneal fluid. Fertil. Steril. 93(8), 2538\u20132544 (2010).","journal-title":"Fertil. Steril."},{"issue":"2","key":"299_CR57","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/S1071-5576(02)00261-7","volume":"10","author":"IM Matalliotakis","year":"2003","unstructured":"Matalliotakis, I. M. et al. Expression of serum human leukocyte antigen and growth factor levels in a Greek family with familial endometriosis. J. Soc. Gynecol. Investig. 10(2), 118\u2013121 (2003).","journal-title":"J. Soc. Gynecol. Investig."},{"key":"299_CR58","first-page":"306830","volume":"2012","author":"G Krikun","year":"2012","unstructured":"Krikun, G. Endometriosis, angiogenesis and tissue factor. Scientifica (Cairo) 2012, 306830 (2012).","journal-title":"Scientifica (Cairo)"},{"key":"299_CR59","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1111\/j.1749-6632.2002.tb02779.x","volume":"955","author":"N Santanam","year":"2002","unstructured":"Santanam, N., Murphy, A. A. & Parthasarathy, S. Macrophages, oxidation, and endometriosis. Ann. N. Y. Acad. Sci. 955, 183\u2013198 (2002).","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"1\u20132","key":"299_CR60","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.jri.2011.08.005","volume":"92","author":"E Sturlese","year":"2011","unstructured":"Sturlese, E. et al. Dysregulation of the Fas\/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis. J. Reprod. Immunol. 92(1\u20132), 74\u201381 (2011).","journal-title":"J. Reprod. Immunol."},{"issue":"5","key":"299_CR61","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1080\/09513590.2019.1683821","volume":"36","author":"AS Lagan\u00e0","year":"2020","unstructured":"Lagan\u00e0, A. S. et al. Evaluation of M1 and M2 macrophages in ovarian endometriomas from women affected by endometriosis at different stages of the disease. Gynecol. Endocrinol. 36(5), 441\u2013444 (2020).","journal-title":"Gynecol. Endocrinol."},{"issue":"2\u20134","key":"299_CR62","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.imbio.2005.05.010","volume":"210","author":"BO Fabriek","year":"2005","unstructured":"Fabriek, B. O., Dijkstra, C. D. & van den Berg, T. K. The macrophage scavenger receptor CD163. Immunobiology 210(2\u20134), 153\u2013160 (2005).","journal-title":"Immunobiology"},{"issue":"4","key":"299_CR63","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/S1357-2725(01)00144-3","volume":"34","author":"JH Graversen","year":"2002","unstructured":"Graversen, J. H., Madsen, M. & Moestrup, S. K. CD163: A signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. Int. J. Biochem. Cell Biol. 34(4), 309\u2013314 (2002).","journal-title":"Int. J. Biochem. Cell Biol."},{"issue":"1","key":"299_CR64","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1182\/blood.V99.1.378","volume":"99","author":"HJ M\u00f8ller","year":"2002","unstructured":"M\u00f8ller, H. J., Peterslund, N. A., Graversen, J. H. & Moestrup, S. K. Identification of the hemoglobin scavenger receptor\/CD163 as a natural soluble protein in plasma. Blood 99(1), 378\u2013380 (2002).","journal-title":"Blood"},{"issue":"5","key":"299_CR65","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1080\/07853890410033171","volume":"36","author":"SK Moestrup","year":"2004","unstructured":"Moestrup, S. K. & M\u00f8ller, H. J. CD163: A regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response. Ann. Med. 36(5), 347\u2013354 (2004).","journal-title":"Ann. Med."},{"issue":"6","key":"299_CR66","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1095\/biolreprod.109.079772","volume":"82","author":"X Zhang","year":"2010","unstructured":"Zhang, X. Hepatocyte growth factor system in the mouse uterus: Variation across the estrous cycle and regulation by 17-beta-estradiol and progesterone. Biol. Reprod. 82(6), 1037\u20131048 (2010).","journal-title":"Biol. Reprod."},{"issue":"2","key":"299_CR67","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1210\/jc.2003-030874","volume":"89","author":"S Yoshida","year":"2004","unstructured":"Yoshida, S. et al. Hepatocyte growth factor\/Met system promotes endometrial and endometriotic stromal cell invasion via autocrine and paracrine pathways. J. Clin. Endocrinol. Metab. 89(2), 823\u2013832 (2004).","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"6143","key":"299_CR68","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/330080a0","volume":"330","author":"K Odink","year":"1987","unstructured":"Odink, K. et al. Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis. Nature 330(6143), 80\u201382 (1987).","journal-title":"Nature"},{"issue":"3","key":"299_CR69","first-page":"510","volume":"72","author":"G Zwadlo","year":"1988","unstructured":"Zwadlo, G., Br\u00fcggen, J., Gerhards, G., Schlegel, R. & Sorg, C. Two calcium-binding proteins associated with specific stages of myeloid cell differentiation are expressed by subsets of macrophages in inflammatory tissues. Clin. Exp. Immunol. 72(3), 510\u2013515 (1988).","journal-title":"Clin. Exp. Immunol."},{"issue":"1\u20132","key":"299_CR70","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cccn.2004.02.023","volume":"344","author":"D Foell","year":"2004","unstructured":"Foell, D., Frosch, M., Sorg, C. & Roth, J. Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation. Clin. Chim. Acta 344(1\u20132), 37\u201351 (2004).","journal-title":"Clin. Chim. Acta"},{"issue":"4","key":"299_CR71","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.4049\/jimmunol.152.4.1888","volume":"152","author":"JM Devery","year":"1994","unstructured":"Devery, J. M., King, N. J. & Geczy, C. L. Acute inflammatory activity of the S100 protein CP-10 Activation of neutrophils in vivo and in vitro. J. Immunol. 152(4), 1888\u20131897 (1994).","journal-title":"J. Immunol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00299-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00299-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00299-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T07:45:02Z","timestamp":1673595902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00299-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["299"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-00299-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]},"assertion":[{"value":"22 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20870"}}