O.N. Merkurieva1, N.E. Kushlinskii2

1,2 Federal State Budgetary Educational Institution of Higher Education «A.I. Evdokimov Moscow State University
of Medicine and Dentistry» of the Ministry of Health of Russia (Moscow, Russia)

Formulation of the problem. Many activators and inhibitors of tumor neoangiogenesis are now recognized by the scientific and medical community as prognostic markers and targets for targeted anti-angiogenic therapy of cancer. Endostatin inhibits endothelial cell proliferation and is a promising marker for tumors of various locations, including bone sarcomas.

The aim of the work is to evaluate endostatin as a biomarker of angiogenesis in malignant bone neoplasms based on a systematic review of the literature on the study of endostatin concentration in blood serum, its expression in the tumor, and the correlation of these parameters with the clinical and morphological characteristics of the disease.

Results. The publications included in this systematic review with meta-analysis demonstrated a statistically significant increase in serum concentrations of endostatin and the level of its expression in the tumor in patients with malignant bone tumors. However, data on the correlation of these laboratory markers and the clinical and morphological characteristics of the tumor are rather contradictory and do not allow one to unequivocally recognize endostatin as an informative biomarker of angiogenesis in bone tumors.

Practical significance. The role of endostatin as a diagnostic and prognostic marker requires further study due to the presence of a small number of publications on this issue in international databases. Therefore, conducting new studies of endostatin in patients with bone sarcomas is a promising direction in laboratory diagnostics and oncoorthopedics.

Merkurieva O.N., Kushlinskii N.E. Endostatin as a biomarker of angiogenesis in patients with bone sarcomas: a systematic review and meta-analysis. Technologies of Living Systems. 2023. V. 20. № 3. Р. 6-16. DOI: https://doi.org/10.18127/j20700997-202303-02 (In Russian).

1. Folkman J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 1971. V. 285. № 21. P. 1182–1186.
2. O'Reilly M.S., Boehm T., Shing Y., Fukai N., Vasios G., Lane W.S., Flynn E., Birkhead J.R., Olsen B.R., Folkman J. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997. V. 88. № 2. P. 277–285.
3. Fletcher C.D., Bridge J.A., Hogendoorn P.C., Mertens F. (ed). Pathology and genetics of tumours of soft tissue and bone. V. 5. 4th ed. WHO. 2013.
4. Solovyev Yu.N. Patologiya opukholey kostey. M.: Prakticheskaya medicina. 2019. 272 s. (in Russian).
5. Unni K.K., Inwards C.Y. Dahlin’s bone tumors: general aspects and data on 10165 cases. Philadelphia: Lippincott Williams & Wilkins. 2006.
6. Koç M., Göçmen E., Kiliç M., Ozbay M., Oktem M., Tez M. Serum endostatin levels in gastric cancer patients: correlation with clinicopathological parameters. Hepatogastroenterology. 2006. V. 53. № 70. P. 616–618.
7. Kantola T., Väyrynen J.P., Klintrup K., Mäkelä J., Karppinen S.M., Pihlajaniemi T. et al. Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers. Br. J. Cancer. 2014. V. 111. № 8. P. 1605–1613.
8. Urunbaev S., Abdikarimov K.G., Polatova D.S. Serum Factors of Angiogenesis and the Growth of Fibroblasts in Osteogenic Sarcoma. Ann. Oncol. 2014. V. 25. № Supplement 4. P. iv509.
9. Dou B., Chen T., Chu Q., Zhang G., Meng Z. The roles of metastasis-related proteins in the development of giant cell tumor of bone, osteosarcoma and Ewing's sarcoma. Technol. Health. Care. 2021. V. 29. S1. P. 91–101.
10. Bi W.Z., Li D.W., Luo S., Song Z.G., Wang Y., Jin H., Wang Y., Li Q., Li M.X., Wang D., Sun B., Xu M., Xu C.X. A high risk of osteosarcoma in individuals who are homozygous for the p.D104N in endostatin. Sci. Rep. 2015. V. 5. P. 16392.
11. Chen Z., Chen Q.X., Hou Z.Y., Hu J., Cao Y.G. Clinical predictive value of serum angiogenic factor in patients with osteosarcoma. Asian Pac. J. Cancer Prev. 2012. V. 13. № 9. P. 4823–4826.
12. Babkina I.V., Osipov D.A., Solovyov Y.N., Bulycheva I.V., Machak G.N., Aliev M.D., Kushlinsky N.E. Endostatin, placental growth factor, and fibroblast growth factors-1 and -2 in the sera of patients with primary osteosarcomas. Bull. Exp. Biol. Med. 2009. V. 148. № 2. P. 246-249.
13. Kim H.S., Lim S.J., Park Y.K. Anti-angiogenic factor endostatin in osteosarcoma. APMIS. 2009. V. 117. Iss. 10. P. 716–723.   
14. Xu C.J., Song J.F., Su Y.X., Liu X.L. Expression of b-FGF and endostatin and their clinical significance in human osteosarcoma. Orthop. Surg. 2010. V. 2. № 4. P. 291–298.
15. Abd El-Rehim D.M., Osman N.A. Expression of a disintegrin and metalloprotease 8 and endostatin in human osteosarcoma: implication in tumor progression and prognosis. J. Egypt. Natl. Canc. Inst. 2015. V. 27. № 1. P. 1–9.