Abstract
Angiogenesis is an important mechanism of tumor development, growth and metastasis in hepatocellular carcinoma (HCC). The poor prognosis of HCC patients has been associated with a failure to detect recurrences following surgery. In the present study, we investigated the association between the patient characteristics and the expression of angiogenic genes to identify early biomarkers of HCC. A comprehensive angiogenic gene expression profile was obtained by paired TaqMan gene array analysis of primary HCC nodules and adjacent non-HCC liver tissue from 12 patients. A total of 14 genes were found to be differentially expressed in HCC liver nodules (>2-fold change); the genes encoding collagen type XVα1, IVα1 and IVα2 were upregulated and the genes associated with vessel growth, neuropilin 2 (NRP2) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) were downregulated. The histopathological analysis revealed that the evolution of HCC nodules from well to poorly differentiated was associated with a 5-fold decrease in LYVE-1 expression, reaching its lowest level early during the transition. The significance of this gene as a biomarker of postoperative survival was demonstrated by a 2-fold decrease in overall survival (OS) rates in the low expression group compared to the high expression group. The multivariate and univariate Cox regression analyses identified LYVE-1 expression as a significant independent prognostic parameter of OS [hazard ratio (HR)=3.067; 95% confidence interval (CI): 1.507-6.273; P=0.0021]. Thus, the results of this study suggested that LYVE-1 expression may constitute a novel early biomarker of postoperative survival in HCC patients.