Angiogenic factors as predictors of survival in patients with bone sarcomas

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Introduction. Primary bone sarcomas are relatively rare neoplasms. They occur predominantly in adolescents and young adults, are characterized by an aggressive clinical course and a high metastatic potential, have a poor prognosis. In this regard, the problem of stratifying the risk of metastasis and death in order to select the optimal treatment tactics always remains relevant. The study of such markers as endostatin, vascular endothelial growth factor (VEGF), insulin-like growth factors IGF-1, IGF-2 as potentially informative predictors of survival in patients with bone sarcomas is pathogenetically determined by their involvement in the processes of tumor growth and metastasis.

Aim – to analyze the relationship between pre-treatment serum levels of endostatin, VEGF, IGF-1 and IGF-2 with overall survival rates in patients with bone sarcomas.

Material and methods. An analysis of overall survival rates was carried out in 134 patients with malignant bone tumors aged from 1 to 73 years (Me=27.0 years; Q1–Q3: 18.0 – 43.0 years), among them 87 men (64.9%) and 47 women (35.1%). All patients comprised 4 groups: osteosarcoma (n=58), undifferentiated pleomorphic sarcoma (n=5), Ewing sarcoma (n=29), chondrosarcoma (n=42). In all of them, before the start of specific antitumor treatment, the levels of endostatin, VEGF, IGF-1, and IGF-2 in the blood serum were determined using enzyme immunoassay. The follow-up period ranged from 1 to 229 months (Me=23.0 months; Q1–Q3: 10.0–121.0 months). To analyze overall survival, life tables and Kaplan–Meier curves were constructed. The effect of the studied serum markers on survival rates was assessed using the logrank test and Cox proportional hazards regression model.

Results. During observation, death occurred in 51 patients (38.1%). In the group of deceased patients, serum levels of endostatin and IGF-2 were statistically significantly increased compared to the group of surviving patients (p<0.001 and p=0.011, respectively). Kaplan-Meier survival analysis using the logrank test revealed statistically significant differences in overall survival between the four groups of patients with different serum levels of endostatin, IGF-1 and IGF-2. The Cox regression method established the prognostic significance of endostatin as a predictor of overall survival (HR=1.012; p=0.013).

Conclusion. Endostatin, IGF-1, IGF-2 can serve as predictors of overall survival of patients with bone sarcomas.

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作者简介

О. Merkureva

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

编辑信件的主要联系方式.
Email: merkureva.o.n@gmail.com
ORCID iD: 0000-0001-6744-005X

Specialist in Laboratory Medicine, Post-graduate Student

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

P. Prishchep

N.N. Blokhin National Medical Research Center of Oncology

Email: Paulig92@mail.ru
ORCID iD: 0000-0003-0810-8238

Post-graduate Student, Pediatric Oncologist, Research Institute of Pediatric Hematology and Oncology

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

I. Kuznetsov

Russian University of Medicine

Email: npkredo@yandex.ru
ORCID iD: 0000-0003-0866-5501

Ph.D. (Biol.), Research Assistant

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

N. Sokolov

S.P. Botkin Moscow Multidisciplinary Scientific and Clinical Center

Email: strivp@mail.ru
ORCID iD: 0000-0002-0706-9575

Ph.D. (Med.), Head Oncology Department of Antitumor Drug Therapy

俄罗斯联邦, 5 2nd Botkinsky pr-d, Moscow, 125284

S. Varfolomeeva

N.N. Blokhin National Medical Research Center of Oncology

Email: s.varfolomeeva@ronc.ru
ORCID iD: 0000-0001-6131-1783

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

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

N. Kushlinskii

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

Email: biochimia@yandex.ru
ORCID iD: 0000-0002-3898-4127

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, 4 Dolgorukovskaya ul., Moscow, 127006; 24 Kashirskoye shosse, Moscow, 115522

参考

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2. Fig. 1. Kaplan–Meier survival curve: а – overall survival of patients with bone sarcomas according to the serum level of endostatin; б – overall survival of patients with bone sarcomas according to the serum level of IGF-1; в – overall survival of patients with bone sarcomas according to the serum level of IGF-2

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