The correlation between low vitamin D status and renal interleukin-6/STAT3 hyper-activation in patients with clear...

Low vitamin D status has been associated with increased risks of renal cell carcinoma (RCC). This study aimed to analyze the link between low vitamin D status and interleukin (IL)-6/STAT3 hyper-activation in clear cell RCC (ccRCC) patients. Forty-three newly diagnosed ccRCC patients and 86 age- and sex-matched controls were recruited. The association between low vitamin D status and IL-6/STAT3 hyper-activation was analyzed. Proliferation makersand STAT3 signal were evaluated. As expected, serum IL-6 level was higher in ccRCC patients than in controls. Moreover, serum IL-6 level was reversely correlated with serum 25(OH)D in ccRCC patients but not in controls. In addition, STAT3 signaling was hyper-activated in cancerous tissue. CcRCC patients were divided into three groups according to serum 25(OH)D level: vitamin D sufficiency (VitD-S, ≥30 ng/ml), vitamin D insufficiency (VitD-I, ≥20 and <30 ng/ml) or vitamin D deficiency (VitD-D, <20 ng/ml). Serum IL-6 was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. Cancerous pSTAT3 level was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The number of pSTAT3⁺ nuclei in cancerous tissue was more in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The expressions of cancerous PCNA, cyclin D1 and Ki-67, three markers of proliferation, were higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The in vitro experiments showed that active vitamin D3 inhibited LPS-induced STAT3 phosphorylation in ACHN cells. Our results provide evidence that low vitamin D status is correlated with hyper-activation of cancerous IL-6/STAT3 and proliferation in ccRCC patients.