Hepatocellular carcinoma (HCC) recurrence after liver transplantation remains a significant clinical problem. Ischemia-reperfusion injury (IRI) occurred inevitably at the early phase after liver transplantation (LT) spawns a significant risk of HCC recurrence. However, their linkage and IRI-derived risk factors for HCC recurrence remain exclusive. Understanding the mechanism of post-transplantation hepatic injury could provide new strategies to prevent the later event of HCC recurrence. We demonstrated that glutathione S-transferase A2 (GSTA2) expression was significantly associated with early phase hepatic and systemic injury and ROS level after liver transplantation. Early phase circulating GSTA2 (_EPCGSTA2) protein was a significant predictor of HCC recurrence and survival. Heterogeneous single nucleotide polymorphism at G335C of GSTA2 was significantly associated with poor survival of HCC recipients. Enhancement of GSTA2 could protect HCC cells against H₂O₂-induced cell death by compensating for the elevated ROS stress. We also demonstrated that GSTA2 played crucial roles in regulating the ROS-associated JNK and AKT signaling pathways and ROS metabolism in HCCs in responding to a dynamic ROS environment. Functionally, endogenous or exogenous upregulation of GSTA2 could promote HCC growth and invasion through activating the epithelial–mesenchymal-transition process. Targeted inhibition of GSTA2 could suppress HCC growth and metastasis. In conclusion, GSTA2 could be a novel prognostic and therapeutic target to combat HCC recurrence after liver transplantation.

肝移植后肝细胞癌（HCC）复发仍然是一个重要的临床问题。在肝移植 (LT) 产生显着的 HCC 复发风险后的早期阶段不可避免地发生缺血-再灌注损伤 (IRI)。然而，它们之间的联系和 IRI 衍生的 HCC 复发风险因素仍然是排他性的。了解移植后肝损伤的机制可以提供新的策略来预防晚期 HCC 复发。我们证明谷胱甘肽 S-转移酶 A2 (GSTA2) 表达与肝移植后早期肝和全身损伤以及 ROS 水平显着相关。早期循环 GSTA2（_EPCGSTA2) 蛋白是 HCC 复发和存活的重要预测因子。GSTA2 的 G335C 处的异质单核苷酸多态性与 HCC 受者的不良存活率显着相关。GSTA2 的增强可以保护 HCC 细胞免受 H ₂ O ₂-通过补偿升高的 ROS 应激诱导细胞死亡。我们还证明 GSTA2 在调节 HCC 中 ROS 相关的 JNK 和 AKT 信号通路和 ROS 代谢以响应动态 ROS 环境中发挥了关键作用。在功能上，GSTA2 的内源性或外源性上调可以通过激活上皮间充质转化过程来促进 HCC 的生长和侵袭。靶向抑制 GSTA2 可以抑制 HCC 的生长和转移。总之，GSTA2 可能是对抗肝移植后 HCC 复发的一种新的预后和治疗靶点。