Endometriosis-Associated Infertility: The Role of Biomarkers of Apoptosis and Proliferation in Early Noninvasive Diagnosis

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Abstract

INTRODUCTION: Endometriosis is a common disease that affects up to 15% of women in the reproductive period and leads to infertility in 25%–50% of cases. The diagnosis of endometriosis is delayed for years due to blurred and diverse clinical presentation, therefore, search for a noninvasive biomarker of endometriosis is an important problem of modern medicine.

AIM: To study the significance of changes in the profile of biomarkers: regulator of Wnt/β-catenin signaling pathway (axis inhibition protein 1; AXIN-1), soluble cytokeratin 19 fragment (cytokeratin fragment antigen 21-1; CYFRA-21-1), cancer antigen 125 (carbohydrate antigen 125; CA-125) in blood plasma of patients with endometriosis-associated infertility (before surgery and in the postoperative period).

MATERIALS AND METHODS: The study included two groups of female patients. The first group consisted of 20 patients of reproductive age with cystic ovarian endometriosis and infertility. All the patients underwent surgical intervention using a laparoscope and a video system, in all the patients the diagnosis of endometriosis was confirmed histologically. Three times in specified periods (before surgery, on the 10th day of the postoperative period, at 6 months), patients with cystic ovarian endometriosis and infertility were taken biomaterial (blood) with further determination of AXIN-1, CYFRA-21-1, CA-125 in blood plasma. The second group consisted of patients of reproductive age with no gynecological pathology. In the second group, biological material (blood) was taken once with further determination of AXIN-1, CYFRA-21-1, CA-125 in blood plasma.

RESULTS: Based on the analysis of the measurement data and comparison of their levels, it was found that the content of the studied AXIN-1, СA-125 biomarkers in patients with cystic ovarian endometriosis and infertility was higher than in patients without gynecological pathology (p < 0.05). As for CYFRA-21-1 biomarker, initially lower values were noted compared to the control group (p < 0.05), however, in the postoperative period, the content of CYFRA-21-1 increased and reached values close to those of healthy patients.

CONCLUSION: Determining the levels of AXIN-1, CYFRA-21-1 apoptosis biomarkers and CA-125 proliferation biomarker in blood of patients with endometriosis-associated infertility gives an insight into the pathophysiological processes in the endometrioid ovarian cysts and may be helpful in development of new noninvasive diagnostic methods and target treatment methods.

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About the authors

Mikhail A. Kiselev

Ryazan State Medical University

Author for correspondence.
Email: michail.kiselev@mail.ru
ORCID iD: 0000-0002-8294-9038
SPIN-code: 7098-2877
Russian Federation, Ryazan

Natalya B. Repina

Ryazan State Medical University

Email: nrepina62@gmail.com
ORCID iD: 0000-0001-5916-3574
SPIN-code: 4119-5550

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Ryazan

Alexander A. Nikiforov

Ryazan State Medical University

Email: a.nikiforov@rzgmu.ru
ORCID iD: 0000-0003-0866-9705
SPIN-code: 8366-5282

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Ryazan

Larisa V. Nikiforova

Ryazan State Medical University

Email: alnik003@yandex.ru
ORCID iD: 0000-0003-4369-0729
SPIN-code: 8735-8565
Russian Federation, Ryazan

Maria N. Dmitrieva

Ryazan State Medical University

Email: dmitrm05@mail.ru
ORCID iD: 0000-0003-0915-026X
SPIN-code: 1083-9650

Cand. Sci. (Pedagogy), Associate Professor

Russian Federation, Ryazan

Ilya A. Usachev

Ryazan Regional Clinical Perinatal Center

Email: usachevi@rambler.ru
ORCID iD: 0000-0003-2257-5297
SPIN-code: 6548-7363
Russian Federation, Ryazan

Anton M. Kiselev

Derzhavin Tambov State University

Email: antonmkiselev@gmail.com
ORCID iD: 0000-0002-8288-1395
SPIN-code: 6719-5527

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Tambov

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Comparison of AXIN-1 levels in the study group (EX1 — before surgery, EX2 — 10th day after surgery, EX3 — 6 months after surgery) and control group.

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3. Fig. 2. Comparison of CYFRA-21-1 levels in women of the study groups (EX1 — before surgery, EX2 — 10th day after surgery, EX3 — 6 months after surgery) and control group.

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4. Fig. 3. Comparison of CA-125 level in women of study groups (EX1 — before surgery, EX2 — 10th day after surgery, EX3 — 6 months after surgery) and control group.

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