Significance of Serum Connective Tissue Growth Factor in Patients with Hepatocellular Carcinoma and Relationship with Angiogenesis

Abstract

Connective tissue growth factor (CTGF) expression changes variously in different human malignancies. The role of CTGF in hepatocellular carcinoma (HCC) is still not clear. The purpose of this study was to investigate the role of serum CTGF in patients with HCC and its correlation with HCC angiogenesis. CTGF, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were measured by ELISA in preoperative sera of 88 patients with HCC with tumor resection and 39 healthy subjects. The relationship between CTGF and HCC clinicopathological parameters was observed. Prognostic significance of CTGF for survival of patients with HCC was assessed by Kaplan-Meier analysis. Preoperative serum CTGF level was significantly higher in patients with HCC than in healthy subjects (median, 63.5 vs. 11.4 ng/ml; P < 0.001). Serum CTGF correlated significantly with a series of clinicopathological parameters (big tumor size, advanced pathological tumor-node-metastasis stage, absence of tumor capsule, portal vein invasion). Serum CTGF showed a significant correlation with disease-free survival and overall survival of patients with HCC. Patients with high serum CTGF (>63.5 ng/ml) had a poorer disease-free survival time than the others (CTGF < or = 63.5 ng/ml; median disease-free survival time, 9.6 vs. 19.3 months). Patients with high serum CTGF had poorer overall survival time (median, 13.1 months) than the others (median, 21.7 months). In multivariate Cox analysis, CTGF was identified as an independent and significant prognostic factor of survival of HCC patients. Serum CTGF plays an important role in the progression of HCC. Serum CTGF may be a potential indicator of angiogenesis of HCC.