The role of some inflammatory markers, cytokins and tumor markers in diagnosis of endometriosis
- serum tumor markers
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Copyright (c) 2022 Jadranka Georgievska, Gligor Tofoski, Goran Dimitrov, Ana Daneva-Markova, Viktorija Jovanovska, Dragi Dabeski, Sashe Jovcevski, Elena Dzikova, Aleksandra Atanasova
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Endometriosis is a multifactorial disease which etiopathogenesis has not been elucidated. One of the theories of etiopathogenesis is the inflammatory theory. Aims of the study: To develop a practical non-invasive test for the diagnosis of endometriosis by examining some inflammatory markers and cytokines; to compare the highly sensitive C-reactive protein (hsCRP), cytokines (interleukin-6-IL-6 and tumor necrotizing factor alpha) and the tumor marker cancer antigen 125 (CA-125) among healthy patients and patients with endometriosis; to determine the sensitivity and specificity of each biomarker separately in the diagnosis of endometriosis and to determine their role in the diagnosis of endometriosis. Materials and methods: In a prospective study conducted at the University Clinic for Gynecology and Obstetrics, Ss. Cyril and Methodius University in Skopje, North Macedonia 138 patients were included of a reproductive age between 18-50 years (83 with diagnosis endometriosis operated laparoscopically or with laparotomy) and a control group of 55 healthy women, in a period between 01.09.2018 to 01.05.2021. Serum levels of IL-6, TNF-α, hs-CRP and tumor marker CA-125 were evaluated in both groups. Results: Serum levels of CA-125, IL-6 and TNF-α and hs-CRP were significantly higher in patients with endometriosis compared to the control group. The surface under the ROC curve (AUC) for IL-6, CA-125, hs-CRP, and TNF-α has shown that as individual markers they all have a discriminatory capacity to diagnose patients with endometriosis. Conclusions: Results obtained in our study showed statistically significantly higher serum concentrations of CA-125, IL-6 and TNF-α and hs-CRP in patients with endometriosis compared to the control group of patients. However, none of these biomarkers showed a high sensitivity for diagnosis of endometriosis. It is necessary to find a panel combination of biomarkers with a high sensitivity of about 100% that will enable early diagnosis of endometriosis.
- Missmer SA, Cramer DW. The epidemiology of endometriosis. Obste Gynecol Clin North Am 2003; 30: 1-19.
- Novak E, Berek JS. Berek-Novak’s gynecology; Lippincott Williams-Wilkins; 2007.
- Duffy JM, Arambage K, Correa FJ et al. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev (4) (2014) CD011031
- Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997; 67: 817-821.
- Sourial S, Tempest N, Hapangama DK. Theories on the pathogenesis of endometriosis. Int J Reprod Med 2014; 2014: 179515
- Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril 2012; 98(3): 511-519.
- Lousse JC, Van Langendonckt A, Defrere S, et al. Peritoneal endometriosis is an inflammatory disease. Front Biosci (Elite Ed). 2012; 4:23-40.
- Malutan M A, Drugan T, Costin N, Ciortea R, Bucuri C, Rada P.M et Mihu D. Pro-inflammatory cytokines for evaluation of inflammatory status in endometriosis. Cent Eur J Immunol 2015, 40 (1): 96-100.
- Sütcü K.H, Celik T.G, Akpak K.Y, Akar E.M, Taskin Ӧ, Ӧzdem S, Uzun G. The value of CA-125, CA 19-9, Interleukin-6, interleukin-8 and HSCRP in the diagnosis of endometriosis. Acta Med Mediterr 2015, 31:793-799.
- Ilie I, Ilie R. Cytokines and endometriosis-the role of immunological alterations. Biotechnology, molecular biology and nanomedicine 2013, 2: 8-19.
- Wu MY, Ho HN. The role of cytokines in endometriosis. Am J Reprod Immunol 2003; 49: 285-296.
- Nisenblat V, Bossuyt PM, Shaikh R, Farquhar C, Jordan V, Scheffers CS et al. Blood biomarkers for non-invasive diagnosis of endometriosis. Cochrane database syst rev 2016; (5): CD012179.
- Amaral VF, Ferriani RA, Sa MF, et al. Positive correlation between serum and peritoneal fluid CA-125 levels in women with pelvic endometriosis. Sao Paolo Med J 2006; 124: 223-227.
- Trojnar K.Ž, Pilszyk A, Niebrzydowska M, et al. The potential of non-invasive biomarkers for early diagnosis of asymptomatic patients with endometriosis. J Clin Med 2021;10(13):2762.
- Airong Shen, Shengnan Xu, Yange Ma, et al. Diagnostic value of serum CA125, Ca19-9 and CA 15-3 in endometriosis: A meta-analysis. J International Med Research 2015; 43(5): 599-609.
- Xavier P, Belo L, Rebelo I, et al. Serum levels of VEGF and TNF-alfa and their association with C-reactive protein in patients with endometriosis. Arch Gynecol Obstet 2006; 273:227-231.
- Lermann J, Mueller A, Körber F et al. Evaluation of high-sensitivity C-reactive protein in comparison with C-reactive protein as biochemical serum markers in women with endometriosis. Fertil Steril 2010; 93(7):2125-2129.
- Irungu S, Mavrelos D, Worthington J, Blyuss O, et al. Discovery of non-invasive biomarkers for the diagnosis of endometriosis. Clin Proteomics 2019; 16:14 .
- May K.E, Conduit-Hulbert S.A, Villar J, et al. Peripheral biomarkers of endometriosis: A systematic review. Hum Reprod Update 2010; 16: 651-674.
- Kashanian M, Sariri E, Vahdat M, et al. A comparison between serum levels of interleukin-6 and CA 125 in patients with endometriosis and normal women. Med J Islam Repub Iran 2015; 29: 280.
- Tian Z, Chang X.H., Zhao Y., et al. Current biomarkers for the detection of endometriosis. Chin Med J 2020; 133:2346-2352.
- Wu M-H, Hsiao K-Y and Tsai Sh-J. Endometriosis and possible inflammation markers. Gynecol Minim Invasive Ther 2015; 4: 61-67.
- Maiorana A, Cicerone C, Niceta M, et al. Evaluation of serum CA 125 levels in patients with pelvic pain related to endometriosis. Int J Biol Markers 2007; 22: 200-202.
- Sütcü HK, Ҫelik GIT, Akrak YK, et al. The value of CA-125, CA 19-9, interleukin-8 and HSCRP in the diagnosis of endometriosis. Acta Med Mediterr 2015; 31: 793.
- Bilibio JP, Souza CA, Rodini GP, et al. Serum prolactin and CA 125 levels as biomarkers of peritoneal endometriosis. Gynecol Obstet Invest 2014; 78:45-52.
- Bedaiwy MA, Falcone T, Sharma RK, et al. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod 2002; 17 (2): 426-431
- Abrao MS, Podgaec S, Filho BM, et al. The use of biochemical markers in the diagnosis of pelvic endometriosis. Hum Reprod 1997; 12: 2523-7.
- Furucu F.N, Sencar L, Ҫetin T.M, et al. Expression of interleukin 6 and tumor necrosis factor alpha in endometriotic tissue: an immunohistochemical study. Cukurova Med J 2020; 45(3):1115-1125.