Up-regulation of microRNA-155 promotes cancer cell invasion and predicts poor survival of hepatocellular carcinoma following liver transplantation

Abstract

MicroRNAs play important roles in cancer development, progression, and metastasis. The aim of this study was to determine whether altered microRNA-155 expression is associated with hepatocellular carcinoma (HCC) recurrence and prognosis following orthotopic liver transplantation (OLT). Tissue specimens from 100 HCC patients following OLT were recruited. MicroRNA-155 expression levels were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of microRNA-155 expression with survival of patients. MicroRNA-155 expression levels of two HCC cell lines (HepG2 and SMMC-7721) and normal liver tissue were quantified using qRT-PCR. The potential function of miR-155 on invasiveness was evaluated in the above HCC cell lines. We found that microRNA-155 expression levels were high in tumor tissues in patients with post-OLT HCC recurrence (n=45) compared with those in patients with non-recurrence (n=55) (P=0.001) and correlated with micro-vascular invasion of HCC tissue samples (P=0.001). Patients with higher miR-155 expression had significantly poorer recurrence-free survival (RFS, log rank P<0.001) and overall survival (OS, log rank P<0.001). Multivariate analysis revealed that high miR-155 expression was an independent predictor of poor prognosis (HR 2.748, P=0.001 for RFS; HR 5.752, P<0.001 for OS). In addition, the invasiveness of HCC cells was significantly increased by higher microRNA-155 expression. MicroRNA-155 is a candidate oncogenic microRNA and plays an important role in promoting HCC cells invasion. Our findings suggest that microRNA-155 may serve as a novel biomarker for tumor recurrence and survival of HCC patients following OLT.