Transducin (Beta)-Like 1 X-Linked Receptor 1 Correlates with Clinical Prognosis and Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.

Abstract

Recent studies have demonstrated that transducin (beta)-like 1 X-linked receptor 1 (TBLR1) is involved in tumor progression. However, the exact role and clinical significance of TBLR1 in hepatocellular carcinoma (HCC) are poorly understood. In this study, we aimed to investigate the expression and clinical significance of TBLR1 in HCC. Quantitative polymerase chain reaction and immunohistochemical staining were performed to detect the expression levels of TBLR1 in HCC tissue and adjacent noncancerous tissue (ANT). The relationships between TBLR1 expression and clinicopathological factors were examined in this study. The effects of TBLR1 on epithelial-mesenchymal transition (EMT) of HCC cells were investigated in vitro. The expression levels of TBLR1 were elevated in HCC cell lines. TBLR1 mRNA in HCC tissue was markedly higher (P<0.001) than that in ANT. High expression of TBLR1 is closely related to serum alpha fetoprotein (P=0.047), BCLC stage (P<0.001), maximum size of tumors (P<0.001), tumor embolus (P<0.001), and histological grade (P<0.001). The disease-free survival and overall survival of HCC patients with high expression of TBLR1 were significantly shorter. Furthermore, we found that EMT of HCC cells could be induced by up-regulating TBLR1 and be inhibited by down-regulating TBLR1. ICG-001, the inhibitor of Wnt/β-catenin signaling, could suppress induction of EMT mediated by TBLR1. Our finding suggested that TBLR1 is likely to be a potential prognostic indicator and therapeutic target for HCC and that TBLR1 may be implicated in EMT of HCC cells.