Down-regulation of formin-like 2 predicts poor prognosis in hepatocellular carcinoma

Abstract

The formin-like 2 protein is a member of the diaphanous-related formin family that controls actin-dependent processes such as cell motility and invasion. This study aimed at clarifying formin-like 2 expression in hepatocellular carcinoma and its correlation with clinicopathologic features and also exploring the effects of formin-like 2 transfection on cell motility and invasion in vitro. Real-time polymerase chain reaction and Western blotting showed that expression of formin-like 2 was lower in 4 hepatocellular carcinoma cell lines than those in normal hepatic epithelial cells (P < .05). Surgical hepatocellular carcinoma samples were taken from patients who had been followed for 5 years. Immunohistochemical analysis revealed down-expression of formin-like 2 in 86 (71.7%) of 120 cases. The expression of formin-like 2 was significantly lower in hepatocellular carcinoma tissues than in adjacent cirrhotic or normal livers (P < .01). Statistical analysis showed that formin-like 2 expression correlated positively with tumor differentiation (P = .046) and vascular invasion (P = .008). Patients whose tumors had lower formin-like 2 expression had shorter overall survival times (P = .040). Multivariate analysis suggested that formin-like 2 expression was a significant and independent prognostic indicator (P = .041). Transient transfection of formin-like 2 suppressed motility and invasion of hepatocellular carcinoma cells in vitro. Our results suggest that formin-like 2 is a valuable marker for the progression of hepatocellular carcinoma. Down-regulation is associated with poor overall survival.