Elevated serum interleukin-35 levels correlate with poor prognosis in patients with clear cell renal cell carcinoma

Increasing evidences have demonstrated that serum interleukin-35 (IL-35) levels are closely associated with the development, progression, and poor prognosis of a variety of cancers. However, the relationship between IL-35 and the progression of human clear cell renal cell carcinoma (ccRCC) are poorly understood. The aim of present study was to assess the expression of IL-35 and determine its clinical significance in human ccRCCs. Enzyme-linked immunosorbent assay (ELISA) was performed to examine the serum IL-35 levels in 132 patients with ccRCC and 100 healthy controls. The association of IL-35 levels with clinicopathological parameters and prognosis of ccRCC patients was statistically analyzed. Serum IL-35 levels in patients with ccRCC (25.86±11.78 pg/ml) were significantly higher than those in healthy controls (10.05±9.47 pg/ml, P<0.001). High serum IL-35 levels were significantly correlated with pathologic stage (P<0.001), fuhrman grade (P<0.001), tumor size (P=0.012), T stage (P=0.007), N classification (P=0.002), metastasis (P<0.001) and recurrence (P=0.001). The Kaplan-Meier survival analysis demonstrated that high serum IL-35 levels were significantly associated with poor overall survival (log-rank, P<0.001). Multivariate analysis demonstrated that serum IL-35 levels (HR=2.919, 95% CI =1.871-4.830, P=0.001) and pathologic stage (HR=2.541, 95% CI =1.227-3.987, P=0.002) were an independent prognostic factor for the overall survival of ccRCC patients. In conclusion, high serum IL-35 levels are associated with poor prognosis in patients with ccRCC. IL-35 may represent a promising and useful prognostic biomarker for ccRCC.