Acute phase circulating micoRNAs predict tumor recurrence and survivals of hepatocellular carcinoma patients after liver transplantation

Abstract

BACKGROUND AND AIM: Tumor recurrence remains a critical issue in liver transplantation for hepatocelluar carcinoma (HCC) patients especially using living donor graft. However, there is a lack of effective prognostic biomarker. We aim to identify acute phase circulating microRNAs (miRNAs), stable molecules in blood, for predicting tumor recurrence and survivals of HCC patients after liver transplantation. METHODS: miRNA-array analysis was performed to compare the plasma miRNA profiles at 2-hour post-transplantation between HCC patients with and without tumor recurrence after liver transplantation. Differential microRNAs were validated by TaqMan real-time RT-PCR among 62 HCC patients at 2-hour post-transplantation and 12 healthy donors. Youden index for predicting tumor recurrence after liver transplantation was determined to classify Low- and High-expression groups for suitable miRNAs. The prognostic values of plasma miRNAs for predicting tumor recurrence and overall and progression-free survivals of patients were examined by statistical analysis. RESULT: Identified by miRNA-array analysis, 14 plasma miRNAs were significantly up-regulated in HCC patients with tumor recurrence after liver transplantation. Statistical analysis of 62 HCC patients showed that high level of plasma mir151-5p (p=0.012), mir215 (p=0.016), mir1246 (p=0.012) or mir1290 (p=0.031) was significantly correlated with tumor recurrence after liver transplantation. Kaplan Meier analysis showed that high level of plasma mir27b (p=0.04), mir122 (p=0.032), mir151-5p (p=0.015), mir192 (p=0.027) or mir1246 (p=0.009) was significantly associated with poor overall survival of patients and high level of mir122 (p=0.028), mir151-5p (p=0.001), mir192(p=0.047) or mir1246 (p=0.001) was significantly associated with progression-free survival. Univariable Cox proportional hazard regression analysis showed that mir151-5p and mir1246 were significant prognostic markers of overall survival (p=0.032 and p=0.024) and progression-free survival (p=0.006 and p=0.005) of HCC patients after liver transplantation. Mir1246 was predicted to target genes involved in tumor suppression, chromatin remodeling, cell cycle and growth. CONCLUSION: Acute phase plasma mir151-5p and mir1246 are potential circulating biomarkers for predicting tumor recurrence and overall and progression-free survivals of HCC patients after liver transplantation.