Increased expression of SPARC and SPARC-like 1 in relation to tumor angiogenesis in hepatocellular carcinoma

Abstract

Background: Tumor angiogenesis, the growth of new blood vessels in tumor, is fundamental to tumor growth and metastasis of tumor cells. Our research group has identified two candidate genes for tumor angiogenesis, SPARC (Secreted Protein Acidic and Rich in Cysteine) and SPARC-like 1, in HCC through gene expression study using cDNA microarray technology. Objective: The aim of the present study was to quantify the expression of SPARC and SPARC-like 1 in HCC and to investigate the relationship between the expression of these genes and the increase in tumor angiogenesis in HCC. Methods: SPARC and SPARC-like 1 mRNA expression in HCC and nontumorous liver of 55 patients was quantitated by real-time RT-PCR. SPARC protein expression was assessed by immunohistochemical staining. The data were then correlated with the result of immunostaining for CD34, which is an endothelial cell marker for HCC angiogenesis. Result: Tumor SPARC mRNA level correlated significantly with tumor SPARC-like 1 mRNA level (p<0.001). Similarly, non-tumor SPARC mRNA level correlated significantly with non-tumor SPARC-like 1 mRNA level (p<0.001). This finding suggested that SPARC and SPARC-like 1 might be co-expressed. Further analysis using paired sample t test indicated that there was a significant difference between tumor and non-tumor SPARC mRNA level (mean 18.54 vs. 4.82, p<0.001). Likewise, there was a significant difference between tumor and non-tumor SPARC-like 1 mRNA level (mean 12.94 vs. 2.87, p<0.001). Immunohistochemical staining data indicated that tumor parenchymal SPARC protein expression was significantly correlated with tumor CD34 immunostaining (p<0.01). Similarly, tumor SPARC-like 1 mRNA expression was also significantly correlated with tumor CD34 immunostaining (p<0.05). Conclusions: Our results indicate that SPARC and SPARC-like 1 are overexpressed in HCC compared with nontumorous liver, and both genes may play a role in HCC angiogenesis.