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-κB, 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-κB, 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-κB р65/р50, VEGF expression and proteases activities are the potential prognostic molecular markers of hematogenic metastasis development in kidney cancers. NF-κB, HIF-1 and VEGF levels can be considered as additional molecular markers predicting the effective pazopanib therapy.
Highlights
The kidney cancer prevalence grows at present worldwide and remains the most aggressive disease among other cancers through its high mortality and poor overall survival
The level of NF-κB p65 is higher in tumors with hematogenic metastases in comparison to the localized form of disease
Coefficient NF-κB p65/p50 has the complex wave-like dynamic: it is high in cancers of patients with single metastasis (3.0 (1.6 - 3.0)) and is decreased in tumors of patients with multiple metastases (0.92 (0.83 - 1.07)), reaching the level of patients with localized disease (0.6 (0.3 - 2.0)
Summary
The kidney cancer prevalence grows at present worldwide and remains the most aggressive disease among other cancers through its high mortality and poor overall survival. Survival is very much related to the stage of cancer when it is diagnosed. Almost 90 percent of kidney cancer patients are still alive after five years if the cancer is discovered before it spreads [1]. This fact is associated with the increase of primary incidence and with involvement of imaging tests such as an ultrasound or a CT scan that can improve the diagnosis [2]. There are no recommended screening tests for kidney cancer in people who are at increased risk [3]
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