Analysis of HIF-1α expression and genetic polymorphisms in human clear cell renal cell carcinoma

Introduction: Clear cell renal cell carcinoma (ccRCC) is mostly diagnosed incidentally and has relatively high recurrence rates. Alterations in VHL/HIF and mTOR pathways are commonly present in ccRCC. The present study attempted to identify potential diagnostic markers at the biochemical and molecular level.Methods: In total, 54 subjects (36 patients with ccRCC and 18 cancer-free controls) were enrolled. ELISA was used to measure the levels of HIF-1 alpha in the tumor and healthy kidney tissue. The association between five selected SNPs (rs779805, rs11549465, rs2057482, rs2295080 and rs701848) located in genes of pathologically relevant pathways (VHL/HIF and mTOR) and the risk of ccRCC in the Slovak cohort was studied using real-time PCR.Results: Significant differences in HIF-1 alpha tissue levels were observed between the tumor and healthy kidney tissue (p < 0.001). In the majority (69%) of cases, the levels of HIF-1 alpha were higher in the kidney than in the tumor. Furthermore, the concentration of HIF-1 alpha in the tumor showed a significant positive correlation with CCL3 and IL-1 beta (p (R2) 0.007 (0.47); p (R2) 0.011 (0.38). No relationship between intratumoral levels of HIF-1 alpha and clinical tumor characteristics was observed. Rs11549465, rs2057482 in the HIF1A gene did not correlate with the expression of HIF-1 alpha either in the tumor or in the normal kidney. None of the selected SNPs has influenced the susceptibility to ccRCC.Conclusion: More research is neccesary to elucidate the role of HIF-1 alpha in the pathogenesis of ccRCC and the association between selected SNPs and susceptibility to this cancer.