Copper and zinc levels in plasma and cancerous tissues and their relation with expression of VEGF and HIF-1 in the pathogenesis of muscle invasive urothelial bladder cancer: a case-controlled clinical study.

To evaluate Cu and Zn levels in bladder cancer (BC) patients and their relationship with expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1). Plasma levels of Cu and Zn were determined in 66 transitional bladder cell carcinoma patients (BC group) and 60 matched controls. The concentration of Cu and Zn as well as the expressions of both VEGF and HIF-1 were also estimated in cancerous and non-cancerous bladder tissues in the BC group. The results showed that plasma Cu and Cu/Zn ratio were significantly higher in BC group when compared with the control group. In contrast, the plasma Zn in BC group was significantly lower than in the controls. Comparing levels of Cu and Zn in cancerous and non-cancerous bladder tissues among the BC group indicated a significantly higher Cu levels in the cancerous tissues, while Zn levels was significantly lower. There were higher expressions of both VEGF and HIF-1 in the cancerous samples. Moreover, the Cu concentration in cancerous tissues was significantly correlated with expressions of VEGF and HIF-1. Logistic regression analysis revealed that the increase in plasma Cu/Zn ratio and plasma Cu and the decrease in plasma Zn may be risk factors for development of bladder cancer. We concluded that alteration of plasma and bladder tissue levels of both Cu and Zn is correlated with pathogenesis of bladder cancer. The increase in Cu level in cancerous tissues of BC group has an important role in angiogenesis in bladder cancer cells.