90P - Neutrophils as producers of endothelial growth factor in the progression of kidney cancer

Background

Neutrophils (Nph) can play both protumor (N2) and antitumor (N1) roles at different stages of carcinogenesis. The tumor microenvironment promotes Nph polarization and enhances pro-angiogenic properties, contributing to changes in serum endothelial growth factor-A (VEGF-A) levels (Amorim C. et al., 2022).The aim of the study was to evaluate the ability of circulating neutrophils to produce VEGF-A during the progression of kidney cancer (KC).

Methods

The object of the study was the blood Nph of patients with KC before treatment, clear cell type I stage (T1N0M0G1, n=28, 60 years), II stage (T2N0M0G2, n=15, 61 years) and III stage (T3N0M0G2, n=15, 63 years) and the control group (n=15, 54 years). RNA was isolated from the peripheral blood Nph fraction on SileksMagNA magnetic particles (Sileks, Russia). The reverse transcription reaction was carried out and the expression of the VEGF-A gene was determined by quantitative PCR using primers (Evrogen, Russia). The level of VEGF-A in serum (pg/ml) was determined by ELISA (Vector-Best-Volga, Russia). The results are presented as Me (Q1-Q3). Statistical processing was performed in Statistica 13 (Mann–Whitney U test, Spearman correlation coefficient (p<0.05)). The study was approved by the Ethics Committee of IME&PK UlSU (protocol No. 1 of 01/15/2020).

Results

We found an increase in the serum level of VEGF-A at all stages of KC (stage I: 227.34 (227.34-399.49), p=0.002; stage II: 337.52 (329.33-692.18), p = 0.0005; III stage: 372.99 (282.99-545.82), p=0.001) relative to the control group (136.34 (91.01-168.95)). This may be due to the development of the angiogenic process during the progression of KC. The absolute amount of Nph decreased depending on the stage of KC: 4.6x10⁹/l at stage I, 3.95x10⁹/l - at stage III, 3.75x10⁹/l - at stage IV. Expression of the VEGF-A gene by circulating Nph did not change at different stages of KC. However, at stage III KC, a correlation was found between VEGF-A gene expression in Nph and the level of this factor in serum (r=0.321, p=0.05).

Conclusions

Our results suggest that circulating Nph in KC has a high potential for VEGF-A production. At the same time, in stage III of KC, the serum level of VEGF-A is associated with an increased release of intracellular VEGF-A from Nph.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.