Increase expression of IL-17A, IL6, STAT3,  TGF-β and VEGF in Bladder Cancer: potential biomarkers?

Abstract

Background: Bladder cancer is the most common urinary system malignant disease all over the world. Our former research results showed that IL-17 family relative cytokines involved in the occurrence and development of bladder cancer, moreover A variety of inflammatory cells (such as lymphocyte, macrophage, mast cell and neutrophil ) infiltrated in bladder cancer tissues and were closely related to bladder cancer.Results: Immunohistochemistry (HIS) was employed to measure expression and location of IL-17A, IL-6, STAT3 and VEGF in pathological specimens of bladder cancer patients with different degree of malignancy (n=80), cystitis (n=23) and relative normal adjacent tissues (n=4). ELISA was used for measuring concentrations of MMP-9, TGF-β, VEGF and IFN-γ in serum samples collected from patients with bladder cancer (n=34) and control subjects (n=5). Immunoreactivity for IL-17A, IL-6, STAT3 and VEGF significant increased in tissues of bladder cancer compared with that of cystitis and normal adjacent tissues (p = 0.001. respectively), which was positively associated with the degrees of malignancy of the cancer. Serum concentrations of TGF-β and VEGF were significantly higher in patients with bladder cancer compared with that of controls (p=0.002 and p=0.0001 respectively), while concentrations of MMP-9 and IFN-γ were not significantly different between the groups of subjects. In the meanwhile, serum concentrations of MMP-9, TGF-β, VEGF, but not IFN-γ were significantly higher in patients with high degree of malignancy (stage Ⅲ and Ⅳ) than that of patients with low malignancy (stage Ⅰ and Ⅱ) (p=0.001, p=0.030, and p=0.011 respectively).Conclusion: Elevated expression of IL-17A, IL-6, STAT3 in tissues and of TGF-β, VEGF in serum might be considered as potential biomarkers for clinical stages of bladder carcinoma progress.Trial registration: ISRCTN, ISRCTN2012BH006. Registered 10 January 2012