Effect of high expression of fatty acid binding protein 5 on prognosis and epithelial-mesenchymal transition in hepatocellular carcinoma.

Abstract

310 Background: Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. The high expression of Fatty Acid Binding Protein 5 (FABP5) has been reported its malignant potential in several cancers. However, the function of FABP5 in HCC remains unknown. We analyzed the correlation between the expression of FABP5 and malignant behavior of HCC using HCC tissues and human HCC cell lines. Methods: A total of 231 HCC samples were obtained through our institute and subjected to immunohistochemical analysis. In vitro, protein expression of FABP5 in HCC cell lines was assessed by Western blot analysis. To the higher FABP5 expression cell lines, we performed proliferation assay, migration assay and invasion assay with or without genetic down-regulation of FABP5 by short hairpin RNA (shRNA). Results: The intensity of immunostaining in HCC tissues was determined comparing to immunoreactivity of Kupffer cells, and the patients were divided into a strong staining group (n=127) and a weak staining group (n=104) according to the intensity of immunostaining. In the strong staining group, 5-year overall survival rate was 58.3%, compared with 90.5% in the weak staining group (p<0.0001). In addition, 5-year relapse free survival rate in the strong staining group was 23.1%, compared with 46.9% in the weak staining group (p<0.0001). Moreover, the strong staining of FABP5 positively correlated with early recurrence, extrahepatic metastasis, AFP, AFP-L3%, PIVKA II, tumor size, poor differentiation, and micro/macro vascular invasion (P<0.05). In vitro, the knockdown of FABP5 significantly inhibited cell proliferation, migration and invasiveness. Additionally, the knockdown of FABP5 was associated with inhibition of epithelial-mesenchymal transition (EMT), including down-regulation of N-cadherin, and Snail converse to the activation of E-cadherin and ZO-1. Conclusions: FABP5 was closely related with the gain of malignant potential through the activation of EMT, and also behaved as a significant prognostic and recurrence factor. Therefore, FABP5 may serve as a new biomarker of HCC and a potential molecular target for the development of HCC therapies.