Molecular biomarkers of endometriosis - options for non-invasive diagnostics?

  • Tea Lanišnik Rižner Institute of Biochemistry Faculty of Medicine University of Ljubljana
Keywords: proteomics, transcriptomics, metabolomics, biomarkers


Endometriosis is a common gynaecological disease defined as a presence of endometrial like tissue outside the uterine cavity. Estimates show that this disease affects up to 10% of premenopausal women and 35%-50% of women with infertility. At present minimal and mild stages of endometriosis can only be unequivocally diagnosed invasively, using laparoscopy. There is thus an urgent need for discovery of biomarkers for non-invasive diagnosis. With the introduction of ‘omics’ methodologies, we have witnessed immense progress in the field of biomarkers of endometriosis. This manuscript overviews different approached for discovery of biomarkers and presents the biomarkers with the highest diagnostic potential.  Current status in the field of endometriosis biomarker discovery and potential for their introduction into clinics are discussed.


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Rogers PA, D'Hooghe TM, Fazleabas A, et al. Defining future directions for endometriosis research: workshop report from the 2011 World Congress of Endometriosis In Montpellier, France. Reprod Sci 2013;20:483-99.

Adamson G, SH K, L H. Creating solutions in endometriosis: global collaboration through the World Endometriosis Research Foundation. J Endometriosis 2010;2:3.

Brosens I, Benagiano G. Endometriosis, a modern syndrome. Indian J Med Res 2011;133:581-93.

Jacques D, Oliver D, Jean-Christophe L, Jean S. Peritoneal, Ovarian, and Rectovaginal Endometriosis are Three Different Entities. In: C GL, H EJL, L HD, eds. Endometriosis Science and Practice. Singapore Markono Print Media Pte Ltd: Willey-Blackwell A John Willey and Sons Ltd.; 2012:92-108.

Hsu AL, Khachikyan I, Stratton P. Invasive and noninvasive methods for the diagnosis of endometriosis. Clin Obstet Gynecol 2010;53:413-9.

Antonio B, Diane D, Anne G, Marco A. Extra-Abdominal Endometriosis. In: C GL, H EJL, L HD, eds. Endometriosis Science and Practice. Singapore Markono Print Media Pte Ltd: Willey-Blackwell A John Willey and Sons Ltd.; 2012:108-17.

Revised American Fertility Society classification of endometriosis: 1985. Fertil Steril 1985;43:351-2.

Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril 2012;98:511-9.

Nap AW. Theories on the Pathogenesis of Endometriosis. In: Giudice LC, Evers JL, Healy DL, eds. Endometriosis Science and Practice. Singapore: Wiley-Blackwell A John Wiley and Sons, Ltd. Publication; 2012:42-53.

Endometrioza - epidemiologija, etiologija, patofiziologija in klasifikacija. In: Ribič-Pucelj M, ed. Endoskopske operacije v ginekologiji. Radovljica: Didakta; 2007:163-7.

May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update 2010;16:651-74.

Ballard K, Lowton K, Wright J. What's the delay? A qualitative study of women's experiences of reaching a diagnosis of endometriosis. Fertil Steril 2006;86:1296-301.

Chamié LP, Blasbalg R, Pereira RM, Warmbrand G, Serafini PC. Findings of pelvic endometriosis at transvaginal US, MR imaging, and laparoscopy. Radiographics 2011;31:E77-100.

Grasso RF, Di Giacomo V, Sedati P, et al. Diagnosis of deep infiltrating endometriosis: accuracy of magnetic resonance imaging and transvaginal 3D ultrasonography. Abdom Imaging 2010;35:716-25.

Fassbender A, Vodolazkaia A, Saunders P, et al. Biomarkers of endometriosis. Fertil Steril 2013;99:1135-45.

Meuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, D'Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril 2009;92:68-74.

Group. BDW. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69:89-95.

Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011;155:529-36.

Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003;3:25.

Huhtinen K, Suvitie P, Hiissa J, et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer 2009;100:1315-9.

Szubert M, Suzin J, Wierzbowski T, Kowalczyk-Amico K. CA-125 concentration in serum and peritoneal fluid in patients with endometriosis - preliminary results. Arch Med Sci 2012;8:504-8.

Van Gorp T, Cadron I, Despierre E, et al. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Br J Cancer 2011;104:863-70.

Vodolazkaia A, Bossuyt X, Fassbender A, et al. A high sensitivity assay is more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis. Reprod Biol Endocrinol 2011;9:113.

Reis FM, Luisi S, Abrao MS, et al. Diagnostic value of serum activin A and follistatin levels in women with peritoneal, ovarian and deep infiltrating endometriosis. Hum Reprod 2012;27:1445-50.

Kocbek V, Vouk K, Mueller MD, Rižner TL, Bersinger NA. Elevated glycodelin-A concentrations in serum and peritoneal fluid of women with ovarian endometriosis. Gynecol Endocrinol 2013;29:455-9.

Mohamed ML, El Behery MM, Mansour SA. Comparative study between VEGF-A and CA-125 in diagnosis and follow-up of advanced endometriosis after conservative laparoscopic surgery. Arch Gynecol Obstet 2013;287:77-82.

Eisenberg VH, Zolti M, Soriano D. Is there an association between autoimmunity and endometriosis? Autoimmun Rev 2012;11:806-14.

Young VJ, Brown JK, Saunders PT, Horne AW. The role of the peritoneum in the pathogenesis of endometriosis. Hum Reprod Update 2013;19:558-69.

Nabeta M, Abe Y, Kagawa L, et al. Identification of anti-α-enolase autoantibody as a novel serum marker for endometriosis. Proteomics Clin Appl 2009;3:1201-10.

Nabeta M, Abe Y, Haraguchi R, Kito K, Kusanagi Y, Ito M. Serum anti-PDIK1L autoantibody as a novel marker for endometriosis. Fertil Steril 2010;94:2552-7.e1.

Nabeta M, Abe Y, Takaoka Y, Kusanagi Y, Ito M. Identification of anti-syntaxin 5 autoantibody as a novel serum marker of endometriosis. J Reprod Immunol 2011;91:48-55.

Yi YC, Wang SC, Chao CC, Su CL, Lee YL, Chen LY. Evaluation of serum autoantibody levels in the diagnosis of ovarian endometrioma. J Clin Lab Anal 2010;24:357-62.

Gajbhiye R, Sonawani A, Khan S, et al. Identification and validation of novel serum markers for early diagnosis of endometriosis. Hum Reprod 2012;27:408-17.

Mihalyi A, Gevaert O, Kyama CM, et al. Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers. Hum Reprod 2010;25:654-64.

Socolov R, Butureanu S, Angioni S, et al. The value of serological markers in the diagnosis and prognosis of endometriosis: a prospective case-control study. Eur J Obstet Gynecol Reprod Biol 2011;154:215-7.

Drosdzol-Cop A, Skrzypulec-Plinta V. Selected cytokines and glycodelin A levels in serum and peritoneal fluid in girls with endometriosis. J Obstet Gynaecol Res 2012;38:1245-53.

Vodolazkaia A, El-Aalamat Y, Popovic D, et al. Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis. Hum Reprod 2012;27:2698-711.

Anastasi E, Granato T, Falzarano R, et al. The use of HE4, CA125 and CA72-4 biomarkers for differential diagnosis between ovarian endometrioma and epithelial ovarian cancer. J Ovarian Res 2013;6:44.

El-Kasti MM, Wright C, Fye HK, Roseman F, Kessler BM, Becker CM. Urinary peptide profiling identifies a panel of putative biomarkers for diagnosing and staging endometriosis. Fertil Steril 2011;95:1261-6.e1-6.

Fassbender A, Waelkens E, Verbeeck N, et al. Proteomics analysis of plasma for early diagnosis of endometriosis. Obstet Gynecol 2012;119:276-85.

Long X, Jiang P, Zhou L, Zhang W. Evaluation of novel serum biomarkers and the proteomic differences of endometriosis and adenomyosis using MALDI-TOF-MS. Arch Gynecol Obstet 2013;288:201-5.

Zheng N, Pan C, Liu W. New serum biomarkers for detection of endometriosis using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Int Med Res 2011;39:1184-92.

Mendrick DL. Transcriptional profiling to identify biomarkers of disease and drug response. Pharmacogenomics 2011;12:235-49.

Teague EM, Print CG, Hull ML. The role of microRNAs in endometriosis and associated reproductive conditions. Hum Reprod Update 2010;16:142-65.

Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008;105:10513-8.

Madhavan D, Cuk K, Burwinkel B, Yang R. Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures. Front Genet 2013;4:116.

Suryawanshi S, Vlad AM, Lin HM, et al. Plasma microRNAs as novel biomarkers for endometriosis and endometriosis-associated ovarian cancer. Clin Cancer Res 2013;19:1213-24.

Wang WT, Zhao YN, Han BW, Hong SJ, Chen YQ. Circulating microRNAs identified in a genome-wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis. J Clin Endocrinol Metab 2013;98:281-9.

Xia J, Broadhurst DI, Wilson M, Wishart DS. Translational biomarker discovery in clinical metabolomics: an introductory tutorial. Metabolomics 2013;9:280-99.

Chace DH, Spitzer AR. Altered metabolism and newborn screening using tandem mass spectrometry: lessons learned from the bench to bedside. Curr Pharm Biotechnol 2011;12:965-75.

Gowda GA, Zhang S, Gu H, Asiago V, Shanaiah N, Raftery D. Metabolomics-based methods for early disease diagnostics. Expert Rev Mol Diagn 2008;8:617-33.

Prieto L, Quesada JF, Cambero O, et al. Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to endometriosis. Fertil Steril 2012;98:126-30.

Khanaki K, Nouri M, Ardekani AM, et al. Evaluation of the relationship between endometriosis and omega-3 and omega-6 polyunsaturated fatty acids. Iran Biomed J 2012;16:38-43.

Vouk K, Hevir N, Ribic-Pucelj M, et al. Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis. Hum Reprod 2012;27:2955-65.

Dutta M, Joshi M, Srivastava S, Lodh I, Chakravarty B, Chaudhury K. A metabonomics approach as a means for identification of potential biomarkers for early diagnosis of endometriosis. Mol Biosyst 2012;8:3281-7.

Chandramouli K, Qian PY. Proteomics: challenges, techniques and possibilities to overcome biological sample complexity. Hum Genomics Proteomics 2009;2009.

Siristatidis CS. What have the 'omics done for endometriosis? Med Sci Monit 2009;15:RA116-23.

Zondervan KT, Cardon LR, Kennedy SH. What makes a good case-control study? Design issues for complex traits such as endometriosis. Hum Reprod 2002;17:1415-23.

Griffith CS, Grimes DA. The validity of the postcoital test. Am J Obstet Gynecol 1990;162:615-20.

Vouk K, Hevir N, Ribić-Pucelj M, et al. Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis. Hum Reprod 2012;27:2955-65.

How to Cite
Lanišnik Rižner T. Molecular biomarkers of endometriosis - options for non-invasive diagnostics?. ZdravVestn [Internet]. 18Dec.2014 [cited 10Dec.2019];83(11). Available from: