CXCL8 is a neutrophil chemotactic factor (Nph), which is a key effector cell of innate immunity and plays a crucial role in various inflammatory diseases. CXCL8 regulates pathological angiogenesis, tumor growth and metastasis and enhances the protumor effect of Nph (Gonzalez-Aparicio M., 2020). At the same time, protumor Nph (N1) are characterized by reduced expression of chemokines (Sagiv J.Y., 2015). The study was aimed at assessing the expression of the CXCL8 gene by circulating Nph and the serum level of CXCL8 at different stages of clear cell kidney cancer.
The study included patients with clear cell kidney cancer (KC) stage I (n=30), stage II (n=15), stage III (n=15) (median age 68 years) and 20 healthy patients (control group) (median age 60). The level of CXCL8 (Vector-Best-Volga, Russia) was determined by ELISA in blood serum. RNA isolation was performed from the peripheral blood Nph fraction using SileksMagNA magnetic particles (Sileks, Russia). After isolation, the reverse transcription reaction was set up. Expression of the CXCL8 gene was determined by quantitative PCR with reverse transcription using primers (Evrogen, Russia). Statistical processing was performed using Statistical 13.
We found a significant decrease in CXCL8 gene expression by circulating Nph in patients with stage I KC compared with the control group (5.97±3.15 vs. 117.42±30.89, p=0.01). In the groups of patients at stages II and III, the change in this indicator was statistically insignificant (1.44±0.56, p=0.078 and 36.97±33.05, p=0.226, respectively). No correlation was found between the expression of this gene by Nph and the stage of KC. Serum CXCL8 levels at all stages of KC were higher than those in the control group (78.79±35.41 - KC stage I, p=0.015; 178.79±98.05 - KC stage II, p=0.001; 68.87±23.92 - KC stage III, p=0.0001 versus 12.61±0.87 in the control group). The association of CXCL8 gene expression in Nph with the serum level of this cytokine was found only in stage I kidney cancer (r=0.804, p=0.0016).
In kidney cancer, circulating Nph are not the main producers of serum CXCL8. An elevated level of CXCL8 probably contributes to the formation of a protumor phenotype of circulating Nph.
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