Soluble form of podoplanin in patients with bone neoplasms

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Introduction. Podoplanin is a mucin-type transmembrane protein involved in the processes of cell migration, angio- and lymphangiogenesis, embryonic development and metastasis. Its biological activity is realized through interaction with partner proteins (CLEC-2, CD44, galectin-8, etc.). Podoplanin expression is detected in various types of normal cells (lymphatic endothelium, podocytes, follicular dendritic cells), and its increase is associated with a number of malignant neoplasms. Of particular interest is the role of podoplanin in the tumor microenvironment and its potential value as a marker for noninvasive diagnostics. The aim of this work is to study the level of soluble podoplanin in the blood serum of patients with primary bone tumors.

Material and methods. The analysis of podoplanin content in the blood serum was performed in 83 patients with malignant bone tumors (MBT), 24 with benign bone tumors (BBT) and 23 healthy donors of the control group. The total group of patients with malignant bone tumors consisted of 19 children aged 6 to 16 years (median 13 years) and 64 adults aged 19 to 76 years (median 50 years). The serum podoplanin level was measured by enzyme immunoassay using the Human Podoplanin Elisa Kit (RayBiotech, USA) according to the manufacturer's instructions. The obtained data were processed using GraphPad Prizm 10.4 software. When comparing the indicators and analyzing their relationships, the nonparametric Mann–Whitney and Kruskal–Wallis tests were used. Differences and correlations were considered statistically significant at p < 0.05.

Results. The podoplanin level in the control group of children was significantly higher than the level in adults (median 219.6 ng/ml versus 12.8 ng/ml). In patients with MBT, the podoplanin level was lower compared to the control (especially in children), but the differences did not reach statistical significance. In the group of adults, a statistically significant decrease in podoplanin was noted in MBT compared to BBT (p = 0.039). ROC analysis showed low diagnostic value of the studied parameter (AUC=0.514 in adults and AUC=0.645 in children). Among patients over 18 years of age, higher podoplanin levels were associated with age under 50 years (p = 0.011). Podoplanin levels were higher in patients with osteosarcoma than with chondrosarcoma (p = 0.071), but the insignificant differences identified were probably due to the age of the patients. In children, no significant correlations were found between podoplanin levels and clinical and morphological parameters.

Conclusions. Measurement of soluble podoplanin levels in serum has no diagnostic value in patients with MBT. The obtained data highlight the limitations of the use of this marker outside the context of tissue expression and indicate the need for further research in this area. The changes in the content of the soluble form of podoplanin that we described depending on age undoubtedly require further study.

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作者简介

N. Kushlinskii

N.N. Blokhin National Medical Research Center of Oncology; Russian University of Medicine

编辑信件的主要联系方式.
Email: biochimia@yandex.ru
ORCID iD: 0000-0002-3898-4127
SPIN 代码: 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

俄罗斯联邦, Kashirskoye shosse, 24, Moscow, 115522; Dolgorukovskaya ul., 4, Moscow, 127006

O. Kovaleva

N.N. Blokhin National Medical Research Center of Oncology

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

Dr.Sc. (Biol.), Research Scientist, Laboratory for the Regulation of Cellular and Viral Oncogenes, Research Institute of Carcinogenesis

俄罗斯联邦, Kashirskoye shosse, 24, Moscow, 115522

A. Alferov

N.N. Blokhin National Medical Research Center of Oncology; Russian University of Medicine

Email: aleksandr.alferov@yahoo.com
ORCID iD: 0000-0003-3585-5693
SPIN 代码: 9252-7995

Ph.D. (Med.), Assistant, Department of Clinical Biochemistry and Laboratory Diagnostics, Clinical Laboratory Diagnostics Physician

俄罗斯联邦, Kashirskoye shosse, 24, Moscow, 115522; Dolgorukovskaya ul., 4, Moscow, 127006

A. Grachev

N.N. Blokhin National Medical Research Center of Oncology

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

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

俄罗斯联邦, Kashirskoye shosse, 24, Moscow, 115522

D. Rogozhin

N.N. Blokhin National Medical Research Center of Oncology

Email: pathol.777@mail.ru
ORCID iD: 0000-0003-0777-9152
SPIN 代码: 8742-7598

Dr.Sc. (Med.), Head of the Department of Morphological and Molecular Genetic Diagnostics of Tumors

俄罗斯联邦, Kashirskoye shosse, 24, Moscow, 115522

A. Kolpaschikov

Russian University of Medicine

Email: kolpaschikov@mail.ru
ORCID iD: 0009-0000-8784-3059
SPIN 代码: 6348-5040

Applicant, Department of Clinical Biochemistry and Laboratory Diagnostics

俄罗斯联邦, Dolgorukovskaya ul., 4, Moscow, 127006

Yu. Kuzmin

Russian University of Medicine

Email: iamgryn@yandex.ru
ORCID iD: 0000-0001-9684-2509
SPIN 代码: 1819-9783

Ph.D. (Biol.), Assistant, Department of Clinical Biochemistry and Laboratory Diagnostics

俄罗斯联邦, Dolgorukovskaya ul., 4, Moscow, 127006

P. Prishchep

N.N. Blokhin National Medical Research Center of Oncology

Email: Paulig92@mail.ru
ORCID iD: 0000-0003-0810-8238
SPIN 代码: 1265-8787

Post-graduate Student, Pediatric Oncologist, L.A. Durnov Research Institute of Pediatric Oncology and Hematology

俄罗斯联邦, Kashirskoye shosse, 24, Moscow, 115522

I. Kuznetsov

Russian University of Medicine

Email: npkredo@yandex.ru
ORCID iD: 0000-0003-0866-5501
SPIN 代码: 8484-9120

Ph.D. (Biol.), Senior Lab Assistant

俄罗斯联邦, Dolgorukovskaya ul., 4, Moscow, 127006

S. Varfolomeeva

N.N. Blokhin National Medical Research Center of Oncology

Email: s.varfolomeeva@ronc.ru
ORCID iD: 0000-0001-6131-1783
SPIN 代码: 5177-1073

Dr.Sc. (Med.), Professor, Director L.A. Durnov Research Institute of Pediatric Oncology and Hematology

俄罗斯联邦, Kashirskoye shosse, 24, Moscow, 115522

I. Stilidi

N.N. Blokhin National Medical Research Center of Oncology

Email: ronc@list.ru
ORCID iD: 0000-0002-0493-1166
SPIN 代码: 9622-7106

Dr.Sc. (Med.), Professor, Academician of the Russian Academy of Sciences, Director

俄罗斯联邦, Kashirskoye shosse, 24, Moscow, 115522

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2. Fig. 1. Analysis of the information content of the podoplanin level: A – comparative analysis of podoplanin content in the blood serum of patients with benign and malignant bone tumors and healthy donors of the control group, taking into account age; Б – ROC analysis for podoplanin in patients with malignant bone tumors (the area under the ROC curve is 0.514 (p=0.871) in the group of patients over 18 years of age and 0.645 (p=0.243) in the group of patients under 18 years of age)

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