Expression and content of VHL in kidney cancer tissue, relationship with clinical and morphological parameters of the disease, expression of transcriptional and growth factors

Abstract

Introduction. The molecular picture of the development of HIF overexpression against VHL deficiency background is a key event associated with the manifestation and progression of clear cell renal cell carcinoma. However, this indicator's significance for the development of the disease and the formation of a response to targeted therapy is not clear. The study aimed to study the relationship between the expression and content of VHL in kidney cancer tissue with clinical, morphological parameters, mRNA level NF-κB p65, NF-κB p50, HIF-1, HIF-2, VEGF, and CAIX. Material and methods. The study included 39 patients with renal cell carcinoma. The disease's localized form (T1-2N0M0) was diagnosed in 20 patients; 19 patients had a disseminated process (T1-3N0-1M1). The study's material was normal, and tumor tissue was obtained during the surgical stage of treatment. VHL expression was determined by real-time PCR. The pVHL protein content was estimated using the Western Blotting method. Results. As a result of the study, it was noted that an increase in the VHL expression, together with a decrease in its protein level, was associated with an increase in tumor size. The prevalence of the disease was accompanied by an increase in both mRNA and VHL content in cancers. There was a negative correlation between the level of VHL expression, the content of the corresponding protein, and a positive association with the expression of NF-κB p65. VHL content in cancers was associated with decreased expression of NF-κB p50, NF-κB p65, and VEGF. Discussion. An increase in VHL expression in tumor tissue promoted the growth of mRNA of transcription factors, in particular NF-κB, which is accompanied by tumor spread. An increase in the VHL protein content led to the suppression of the mRNA level of transcriptional and growth factors, which is probably associated with their inactivation, including through proteasome cleavage, and is an important stage in oncogenesis. Conclusion. The relationship between the expression and content of the VHL protein is of decisive importance in the development of the disease, the formation of distant metastases.