212.3 GSTA2 Promotes Liver Tumor Recurrence after Liver Transplantation through Regulating ROS Metabolism Kevin Tak-Pan Ng, Lynn Yin-Fan Lam, Matthew Lau, Xiang Qi, Xiao Bing Liu, Oscar Wai-Ho Yeung, Yuen Yuen Ma, Hui Liu, Jiang Liu, Chung Mao Lo, Kwan Man Department of Surgery, the University of Hong Kong, Hong Kong, People's Republic of China. Introduction: Tumor recurrence remains a major obstacle in hepatocellular carcinoma (HCC) recipients after liver transplantation. Our previous studies have indicated that elevated hepatic injury at early-phase after liver transplan- tation promotes late-phase tumor progression and invasion [1][2] . GSTA2 was identified to be significantly upregulated in early-phase of HCC recipients who developed with tumor recurrence in late-phase. We aimed to investigate the prognostic value of circulating GSTA2 in predicting tumor recurrence after liver transplantation and explore its underlying molecular mechanism. Methods: Post-transplantation plasma GSTA2 protein of 70 HCC recipients was examined by ELISA analysis. The prognostic value of plasma GSTA2 in predicting tumor recurrence and survival was examined by statistical analy- ses. The expression level of GSTA2 and ROS-associated genes was exam- ined by real-time RT-PCR. Suppression of GSTA2 in HCC cell lines was established by lentiviral approach. The roles of GSTA2 in regulating HCC pro- liferation, metastasis and ROS metabolism were studied by in vitro and in vivo functional assays. The effect of GSTA2 in regulating other ROS-associated genes was studied by by RT 2 Profiler PCR array. Results: Higher level of plasma GSTA2 at early-phase after liver transplan- tation significantly predicted tumor recurrence of HCC recipients (Sensitiv- ity = 0.875; specificity = 0.481; P = 0.031) (Fig.1A). Higher level of plasma GSTA2 was also significantly associated with poor overall (P = 0.041) and dis- ease-free survival (P = 0.024) of HCC recipients (Fig. 1B and 1C). The ex- pression level of hepatic GSTA2 after liver transplantation was significantly correlated with ROS-associated genes such as GPX2 and SOD3. Suppres- sion of GSTA2 in HCC cells significantly inhibited in vitro and in vivo prolifera- tion and metastasis of HCC cells. Upregulation of GSTA2 could compensate H 2 O 2 -induced high ROS stress and damage in both normal liver and HCC cells. Alteration of GSTA2 expression in HCC cells could influence the expres- sion level of several ROS-associated genes such as NCF1, SOD3, MT3, MBL2, ALB, TPO and GPX5. Conclusion: Post-transplantation circulating GSTA2 is a potential bio- marker for predicting tumor recurrence and survival of HCC recipients af- ter liver transplantation. Higher level of GSTA2 after liver transplantation could promote tumor recurrence through regulating ROS metabolism. References: 1. Man K, Lo CM, Xiao JW, Ng KT, Sun BS, Ng IO, Cheng Q, Sun CK, Fan ST. The significance of acute phase small-for-size graft injury on tumor growth and invasiveness after liver transplantation. Ann Surg 2008;247: 1049-57. 2. Man K, Shih KC, Ng KT, Xiao JW, Guo DY, Sun CK, Lim ZX, Cheng Q, Liu Y, Fan ST, Lo CM. Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts. Ann Surg 2010;251: 1154-61. FIGURE 1. Early-phase circulating GSTA2 in predicting post-transplanta- tion late-phase tumor recurrence and survival of HCC recipients. S50 Transplantation ■ May 2017 ■ Volume 101 ■ Number 5S-3 www.transplantjournal.com Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.