Signaling pathway components of immune checkpoint PD-1/PD-L1 in blood plasma of patients with ovarian cancer and benign ovarian tumors: clinical and morphological correlations


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Abstract

Objective. To analyze the contents of soluble programmed cell death receptor and its ligand (sPD-1/sPD-L1) in blood plasma of patients with ovarian cancer taking into consideration the main clinical and morphological characteristics of the disease. Materials and methods. A total of125 patients with ovarian neoplasms were enrolled in the study, including 94patients with ovarian cancer, 22 patients with benign tumors and 9 patients with borderline ovarian tumors. The age of the patients was 18-78 years. The control group consisted of 34 healthy women aged 18-68 years. Before treatment all patients were performed the analysis of sPD-1 and sPD-L1 levels in blood plasma using standard ELISA kits (Affimetrix, eBioscience, USA) according to the manufacturer’s instructions. Measurements were performed with immunoassay analyzer BEP 2000Advance (Siemens, Germany). Results. The level of plasma sPD-L1 in patients with ovarian cancer does not differ significantly from one in the control group, while this level is significantly lower in patients with benign tumors than in healthy controls and patients with ovarian cancer. The level of sPD-1 in patients with ovarian cancer is increased as compared to the healthy controls (p=0.03). There is no correlation of marker levels with the histological structure and degree of differentiation of ovarian cancer. The level of sPD-L1 rises with the increasing stage of the disease (p<0.001); it is significantly higher in patients with ascites and bilateral ovarian lesions than in patients without ascites and unilateral lesions. The level of sPD-1 does not depend on the prevalence of ovarian cancer. Conclusion. The level of plasma sPD-L1 in patients with ovarian cancer correlates with the prevalence of the process and can be considered as a marker for monitoring anti-PD1/PD-L1 therapy. The clinical significance of sPD-1 is an important issue for future research.

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About the authors

Nikolay E. Kushlinskii

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: kne3108@gmail.com
MD, Professor, Member of the Russian Academy of Sciences, Head of the Laboratory of Clinical Biochemistry

Elena S. Gershtein

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: esgershtein@gmail.com
PhD, Doctor Biol. Sci, Professor, Leading Researcher, Laboratory of Clinical Biochemistry

Dmitry O. Utkin

A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia

Email: utkindo@yandex.ru
applicant

Natalya A. Petrikova

Ryazan Regional Clinical Oncology Dispensary

Email: petrikova.nat@yandex.ru
Pathologist, Department of Pathologic Anatomy with Pathomorphologic Laboratory

Dmitry N. Kushlinskiy

A.F. Tsyb Medical Radiological Research Center - Branch of the National Medical Research Center of Radiology

Email: drkushlinskiy@gmail.com
senior researcher, Department of combined and surgical methods of treatment of gynecological diseases

Mikhail A. Shabanov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: 0l52@mail.ru
MD, Professor, leading researcher, Department of morphologic and molecular genetic tumor diagnostics

Marina M. Khulamkhanova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: marina_2705@list.ru
oncologist

Lev A. Ashrafyan

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: Levaa@yahoo.com
MD, Professor, Member of the Russian Academy of Sciences, Director of the Institute of Oncogynecology and Mammology

Ivan S. Stilidi

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: Stylidi@ronc.ru
MD, Professor, Member of the Russian Academy of Sciences, director

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