Zhang Rulin, Wu Junyi, Yang Yiming, Xia Dongge, Li Jiayong, Quan Heng, Niu Ziguang, Yang Ye, Wu Jun
Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
J Cancer. 2020 Mar 4;11(10):3082-3088. doi: 10.7150/jca.39712. eCollection 2020.
: Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between Rap1A gene rs494453 polymorphism and HCC. However, the relationship between Rap1A rs494453 polymorphism and HCC recurrence after LT remained unclear. : A total of 74 HCC patients who underwent LT from July 2005 to June 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as Rap1A rs494453. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The Rap1A rs494453 genotype frequencies were determined using the Χ² test and the minor allele frequencies (MAFs) of Rap1A rs494453 genotypes were calculated by Hardy-Weinberg equilibrium. : We found that the donor Rap1A rs494453 polymorphism was profoundly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and donor Rap1A rs494453 genotype were proved to be independent risk factors for HCC recurrence. Patients with donor AG/GG genotypes had a distinct lower RFS and OS than AA genotype. The TNM stage, Milan criteria, microvascular invasion, and donor Rap1A rs494453 genotype were independent factors for the RFS of LT patients. : Donor Rap1A rs494453 is a potential predictive marker for HCC recurrence risk after LT.
肝细胞癌（HCC）复发在肝移植（LT）后很常见，严重影响患者的长期生存。既往研究证实Rap1A参与肝癌发生和转移，并表明Rap1A基因rs494453多态性与HCC之间存在显著关联。然而，Rap1A rs494453多态性与LT后HCC复发的关系仍不清楚。
对2005年7月至2015年6月期间接受LT的74例HCC患者进行分析。供体和受体的基因型均已确认为Rap1A rs494453。采用单因素和多因素logistic回归分析研究与HCC复发相关的独立危险因素。采用Cox回归分析计算无复发生存期（RFS）和总生存期（OS）。使用χ²检验确定Rap1A rs494453基因型频率，并通过Hardy-Weinberg平衡计算Rap1A rs494453基因型的次要等位基因频率（MAF）。
我们发现供体Rap1A rs494453多态性与LT后HCC复发密切相关。此外，米兰标准、微血管侵犯和供体Rap1A rs494453基因型被证明是HCC复发的独立危险因素。供体AG/GG基因型患者的RFS和OS明显低于AA基因型患者。TNM分期、米兰标准、微血管侵犯和供体Rap1A rs494453基因型是LT患者RFS的独立因素。
供体Rap1A rs494453是LT后HCC复发风险的潜在预测标志物。
