Receptors of vessel endothelial growth factor 1 and 2 type at significant interleukin-16 levels in the serum of the blood of patients with new bone formations

Relevance. The results of molecular biological studies served as the basis for conducting a clinical study on the possibility of using antiangiogenic drugs in the treatment of bone sarcomas. Their mechanism of action is to inhibit tyrosine kinases involved in tumor growth, including inhibiting the binding of a key activator of neoangiogenesis of vascular endothelial growth factor (VEGF) with its type 1 and 2 receptors (VEGFR1, VEGFR2), which leads to a decrease in vascularization and inhibition tumor growth. In addition to VEGF, other biologically active substances, including the interleukin-16 cytokine (IL-16), are also involved in tumor neoangiogenesis activators. Goal. Comparative study of the initial levels of VEGFR1 and VEGFR2 receptors in the serum of patients with malignant, borderline and benign bone neoplasms with significant levels of IL-16 and their role in the bone sarcomas prognosis. Material and methods. We examined 138 patients with bone tumors (malignant - 106; benign - 10; borderline (giant cell tumor) - 22). The markers were studied by an enzyme immunoassay method in the blood serum of patients before the specific treatment with Biosource (USA) reagents - IL-16 and "R & D" (USA) - VEGFR1 and VEGFR2. Statistical processing of the results was performed using the program "Statistica 7.0". Results. Significant levels of IL-16 were detected in serum samples of 93% of patients with bone neoplasms. Differences in the content of IL-16 in the serum with regard to the morphological structure of the tumor was not detected. In typical osteosarcoma and Ewing's sarcoma, serum levels of VEGFR1 and VEGFR2 are significantly higher than in chondrosarcoma (p = 0.0003 and p = 0.00009; and p = 0.032 and p = 0.005, respectively). The serum levels of VEGFR1 and VEGFR2 in patients with bone tumors were significantly higher at baseline levels of IL-16 <33.0 pg / ml than in patients with high levels of IL-16 > 33.0 pg / ml (p = 0.027 and p = 0.026 respectively). A significant direct relationship was found between serum levels of VEGFR1 and VEGFR2 (r = 0.34, p = 0.002). The overall 5-year survival in the entire group was 56%. The overall 5-year survival in the entire group was 56%. With a combination of IL-16 <33 pg / ml and VEGFR2 <11.3 ng / ml, the overall 5-year survival was 85%, whereas at high IL-16 values >33 pg / ml and low VEGFR2 < 11.3 ng / ml - it was equal to 25%. The overall 5-year survival rate in the presence of all high values of IL-16, VEGFR1, VEGFR2 in the blood was 67%, for all low values of marker - 78%. It should be noted that with a combination of levels of IL-16> 33.0 pg / ml, VEGFR1 <108.5 pg / ml, VEGFR2 >11.3 ng / ml and IL-16 <33.0 pg / ml, VEGFR1 >108, 5 pg / ml, VEGFR2 <11.3 ng / ml -the indicators of total 5-year survival were maximum - 100%. The worst outcomes of overall 5-year survival (0%) were observed with a combination of IL-16 >33.0 pg / ml, VEGFR1 >108.5 pg / ml, VEGFR2 < 11.3 ng / ml and IL-16 <33, 0 pg / ml, VEGFR1 <108.5 pg / ml, VEGFR2 >11.3 ng / ml. Conclusion. The results indicate the promise of conducting studies on the content of IL-16, VEGFR1 and VEGFR2 in the peripheral blood of patients with bone neoplasms for studying the possibility of their use as prognostic markers.

IL-16, VEGFR1, VEGFR2, IL-16, VEGFR1, VEGFR2, bone sarcomas, overall survival