Comparative analysis of P-cadherin levels in the blood serum of patients with ovarian neoplasms, taking into account their clinical and morphological characteristics

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Abstract

Introduction. Cadherins are a family of calcium-dependent transmembrane glycoproteins that mediate specific cell-cell adhesion via homophilic interactions between their extracellular domains. They play a key role in the formation of cell-cell contacts, maintenance of tissue architecture, and regulation of cell polarity. Disturbances in the expression or function of cadherins are closely associated with the processes of epithelial-mesenchymal transition, invasion and metastasis of tumor cells. In addition to full-length membrane forms, cadherins can exist as soluble fragments (s-cadherins) circulating in the extracellular space or biological fluids, including blood serum. Currently, the biological and clinical significance jf the soluble form of P-cadherin (sP-cadherin) remains poorly understood. Literature data on the concentration and diagnostic or prognostic value of sP-cadherin in malignancies are extremely limited, highlighting the need for further research in this area.

The aim of the work is to analyze the potential clinical significance of sP-cadherin as a diagnostic marker for benign, borderline and malignant ovarian tumors.

Material and methods. The study included 105 patients with primary epithelial ovarian cancer (median age 58 years), 11 patients with borderline ovarian tumors (median age 56 years), 15 patients with benign ovarian tumors (median age 49 years) and 21 practically healthy women in the control group (median age 61 years), who underwent examination and treatment in the period from 2023 to 2025. The concentration of sP-cadherin was determined in the blood serum before the start of specific treatment using the Human P-Cadherin ELISA Kit (RayBiotech, USA). When comparing the indicators and analyzing their relationships, the nonparametric Mann-Whitney and Kruskal-Wallis tests were used. The analysis of the informativeness of the diagnostic method by assessing its sensitivity and specificity was carried out by constructing ROC curves and calculating the area under them (AUC).

Results. It was found that the median level of sP-cadherin in patients with ovarian cancer (8.45 ng/ml) was statistically significantly higher than the control group (3.22 ng/ml; p = 0.000002), patients with borderline ovarian tumors (3.07 ng/ml; p = 0.0012) and benign ovarian neoplasms (4.27 ng/ml; p = 0.03). ROC analysis demonstrated moderate diagnostic accuracy for differentiating malignant ovarian tumors from a control group of healthy women at a threshold serum marker level of 5.75 ng/ml; the test sensitivity was 72.4%, specificity 71.4% (AUC = 0.826; Youden index 0.438). sP-cadherin showed limited diagnostic value in borderline and benign ovarian tumors. No significant differences in sP-cadherin levels were found in subgroups of ovarian cancer patients based on stage, histological type, presence of metastases and ascites, and tumor differentiation grade.

Conclusions. A significant increase in the level of sP-cadherin in the blood serum of patients with epithelial ovarian cancer was revealed, compared with controls, borderline and benign ovarian tumors, which indicates the potential diagnostic significance of this marker. Median sP-cadherin concentrations did not differ between controls, patients with borderline and benign ovarian tumors. No significant association of sP-cadherin levels with the main clinical and morphological characteristics of ovarian cancer was found. It is necessary to continue studying sP-cadherin in patients with ovarian cancer as a diagnostic marker in multiparametric panels and validation in expanded cohorts of patients.

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About the authors

S. Yu. Nezhdanova

Russian University of Medicine of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: nezhdsveta@ya.ru
ORCID iD: 0009-0000-8746-7217
SPIN-code: 1584-0091

Applicant, Department of Clinical Biochemistry and Laboratory Diagnostics

Russian Federation, Delegatskaya Street, 20/1, Moscow, 127473

O. V. Kovaleva

N.N. Blokhin National Medical Research Center of Oncology

Email: ovkovaleva@gmail.com
ORCID iD: 0000-0001-6132-9924
SPIN-code: 9912-4482

Dr.Sc. (Biol.), Researcher, Laboratory for the Regulation of Cellular and Viral Oncogenes

Russian Federation, Kashirskoye shosse, 24, Moscow, 115522

A. N. Grachev

Skolkovo Institute of Science and Technology

Email: alexei.gratchev@gmail.com
ORCID iD: 0000-0003-2137-1866
SPIN-code: 9661-2601

Dr.Sc. (Biol.), Head of the Laboratory of Tumor Stromal Cell Biology

Russian Federation, Bolshoy Boulevard, 30, building 1, Skolkovo Innovation Center, Moscow, 121205

S. E. Kulikova

Russian University of Medicine of the Ministry of Health of the Russian Federation

Email: s_s76@mail.ru
ORCID iD: 0009-0000-1463-4563
SPIN-code: 8958-3123

Laboratory Assistant of the Department of Clinical Biochemistry and Laboratory Diagnostics

Russian Federation, Delegatskaya Street, 20/1, Moscow, 127473

N. E. Kushlinskii

Russian University of Medicine of the Ministry of Health of the Russian Federation; N.N. Blokhin National Medical Research Center of Oncology

Email: biochimia@yandex.ru
ORCID iD: 0000-0002-3898-4127
SPIN-code: 6225-1487

Dr.Sc. (Med.), Professor, Academician of the Russian Academy of Sciences, Scientific Director of the Clinical Diagnostic Laboratory, Head of the Department of Clinical Biochemistry and Laboratory Diagnostics

Russian Federation, Delegatskaya Street, 20/1, Moscow, 127473; Kashirskoye shosse, 24, Moscow, 115522

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Frequency of detection of elevated serum marker levels relative to the control (cadherin-P concentration threshold was 4.7 ng/ml) in the general group of patients with ovarian neoplasms (cancer + borderline + benign tumors)

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3. Fig. 2. ROC curve for P-cadherin concentrations in the blood serum of the general group of patients with ovarian neoplasms and healthy women in the control group

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4. Fig. 3. ROC curve for P-cadherin concentrations in the blood serum of patients with ovarian malignancies and healthy women in the control group

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5. Fig. 4. ROC curve for P-cadherin concentrations in the blood serum of patients with malignant ovarian neoplasms and the general group of borderline + benign ovarian tumors

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