Clinical significance of circulating IL-10 and fibronectin levels in hepatocellular carcinoma patients with HBV infection

Abstract

Hepatocellular carcinoma (HCC) is the major cause of cancer-related death in Taiwan and is strongly associated hepatitis B virus (HBV) infections. Previous studies observed an imbalanced T-helper (Th)1/Th2 cytokine profile in HCC patients, however, less attention has been paid to the variation of Th2 cytokines, anti-inflammatory cytokines such as IL-4 and IL-10, in HCC patients. Increased expression of Fibronectin, VEGF and TGF-β1 in HCC patients has been observed, the relationship between these factors and other biomarkers remains unknown. This study examined the clinical significance of circulating interleukin-10 and fibronectin levels in HBV-infected hepatocellular carcinoma (HCC) patients. HCC patients were classified according to international tumor-node-metastasis staging system as I ( n = 8), II ( n = 24), III ( n = 20) and IV ( n = 10). Thirty healthy subjects were included as control group. Compared with the control group, 7 test cytokines [interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10, interferon-γ and tumor necrosis factor (TNF)-α] were significantly higher in HCC patients ( p < 0.05). Plasma TNF-α concentration in HCC patients increased from stage to stage ( p < 0.05), while concentrations of both IL-4 and IL-10 decreased from Stage II to Stage IV ( p < 0.05). HCC patients also had significantly higher plasma levels of VEGF, TGF-β1 and fibronectin than the control group ( p < 0.05). Within HCC groups, both vascular endothelial growth factor (VEGF) and fibronectin levels decreased in Stage IV. VEGF, transforming growth factor-β1 (TGF-β1) or fibronectin were negatively correlated with IL-10, and the correlation coefficients were lower than e0.7. Both VEGF and TGF-β1 were positively correlated with fibronectin, and the correlation coefficients were higher than 0.7. The circulating levels of IL-10 and fibronectin may reflect progression of HCC. Thus, monitoring these biomarkers may benefit HCC progression evaluation.