Evaluation of notch and hypoxia signalling pathway in human renal cell carcinoma.

Abstract

e21088 Background: Notch genes play a critical role in growth, development and tumorigenesis. HIF1-α can interact with the Notch intracellular domain to augment the Notch downstream response. Because the Notch signalling pathway is responsive to hypoxia we examined, in this study, the patterns of expression and clinical significance of Notch, Notch receptors and Hif1-α and β in human renal cell carcinoma paraffin-embedded tissues. Methods: Eighty cases of renal cell carcinoma (RCC) tissues were detected by immunohistochemistry. RNA of quality only was obtained in 60 samples (80% clear RCC, 10% papillary RCC and 10% chromophobe RCC) to carry out the study of gene expression through qPCR (quantitative real-time polymerase chain reaction). A pool of normal kidney-derived RNA samples (N=5) was used as healthy control. GAPDH and YWHAZ were used as reference genes. GenEx software was used for qPCR data processing and analysis. Results: Mann-Whitney's U test nonparametric statistical analysis showed: Hif1- α, Hif1- β, Notch1 and Notch3 were upregulated in chromophobe RCC (p=0.045, p=0.03, p=0.03 and p=0.02 respectively). Hif1- α and Notch3 were upregulated in clear RCC (p=0.034 and p=0.041 respectively). Spearman's correlation coefficient showed a strong positive correlation between Nocth1-4 members and their receptors and Hif1-α and β genes. Highlight the correlation found between: Notch1 and Hif1-α (Spearman's rho = 0.740, significance level 0.01) and Hif1-β and Jagged1 (Spearman's rho = 0.752, significance level 0.01). Conclusions: Our findings indicated that the co-expression of Notch receptors, their ligands and Hif-1 α and Hif1- β subunits may play a role in human RCC. Notch cascade may represent a novel and therapeutically accessible pathway in chromophobe and clear RCC. More detailed studies of these crossing pathways should be continued in the future.