Molecular Markers of Kidney Cancer Progression, Association with Efficiency of Pazopanib Therapy

Abstract

Purpose: The aim of the study is to reveal associations between NF-κB, HIF-1alpha, VEGF expres-sions, proteasome and calpain activities with tumor progression in patients with kidney cancers and to find molecular parameters, associated with the effective pazopanib therapy. 93 patients with clear cell kidney cancers are included in investigation. 26 patients with disseminated kidney cancer have the pazopanib therapy. Methods: Transcription factors, VEGF, VEGFR2 and p-m-TOR expression are measured by ELISA kits. Proteasome and calpain activity are determined using specific fluorogenic substrate. Results: It is found the increase of NF- κ B, HIF-1 expression in cancer tissues followed the hematogenic metastasis development. Coefficient NF-κB р65/р50 and VEGF expression are increased in cancer tissues with single metastasis and are decreased in cancer tissues with multiple ones. It is observed in the low proteasome activity in metastatic cancer tissues. The partial cancer regression is revealed in 29.6% of patients treated with pazopanib, cancer stabilization—in 61.5% of patients and cancer progression—in 11.5% of patients. The increased level of transcription factors NF- κ B, HIF-1, growth factor VEGF and high proteasome activity in cancer tissues before targeted therapy are associated with the effective treatment. It is obtained the significant decrease of investigated markers after pazopanib application in metastatic kidney cancer patients. Conclusion: Coefficient NF- κ B р65/р50, VEGF expression and proteases activities are the potential prognostic molecular markers of hematogenic metastasis development in kidney cancers. NF- κ B, HIF-1 and VEGF levels can be considered as additional molecular markers predicting the effective pazopanib therapy.