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供体白细胞介素6基因多态性可预测肝移植后肝细胞癌的复发。

Donor interleukin 6 gene polymorphisms predict the recurrence of hepatocellular carcinoma after liver transplantation.

作者信息

Chen Dawei, Liu Shuanghai, Chen Sheng, Wang Zhaowen, Wu Zehua, Ma Kai, Fan Junwei, Peng Zhihai

机构信息

Department of Hepatopancreatobiliary Surgery, Jiangyin People's Hospital, School of Medicine, Southeast University, Jiangyin, China.

Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 100, Haining Road, 200080, Shanghai, China.

出版信息

Int J Clin Oncol. 2016 Dec;21(6):1111-1119. doi: 10.1007/s10147-016-1001-1. Epub 2016 Jul 1.

Abstract

BACKGROUND

Application of the Milan criteria is an effective strategy to select patients with hepatocellular carcinoma (HCC) for liver transplantation, but HCC recurrence is still a major concern. The aim of this study was to determine whether interleukin 6 (IL6) polymorphisms and clinical variables are potential predictors for HCC recurrence and prognosis after transplantation.

METHODS

A total of 110 consecutive patients with HCC undergoing liver transplantation were enrolled in the study. Six tag single nucleotide polymorphisms in IL6 were genotyped in both the donors and recipients. Demographic characteristics, HCC features, and IL6 polymorphisms were assessed against HCC recurrence.

RESULTS

Pretransplant hepatitis B virus DNA (P = 0.014), pretransplant serum alpha-fetoprotein (P = 0.035), number of nodules (P = 0.011), diameter of main nodule (P = 0.001), macrovascular invasion (P = 0.001), microvascular invasion (P = 0.001), HCC exceeding the Milan criteria (P < 0.001), and donor rs2069852 AA genotype (P = 0.010) were associated with HCC recurrence. Recurrence-free survival rate and overall survival rate were significantly lower (P = 0.011 and P = 0.026, respectively) in patients whose donor had the rs2069852 AA genotype than in those whose donor had the AG and GG genotypes. Independent risk factors for recurrence-free survival and overall survival were microvascular invasion (P = 0.003; P = 0.002), HCC exceeding the Milan criteria (P < 0.001; P = 0.001), and donor rs2069852 AA genotype (P = 0.002; P = 0.010).

CONCLUSIONS

Our data suggest that donor IL6 rs2069852 polymorphisms may be a potential genetic marker for HCC recurrence after liver transplantation in the Han Chinese population.

摘要

背景

应用米兰标准是选择肝细胞癌(HCC)患者进行肝移植的有效策略,但HCC复发仍是主要关注点。本研究旨在确定白细胞介素6(IL6)基因多态性和临床变量是否为移植后HCC复发及预后的潜在预测指标。

方法

共纳入110例连续接受肝移植的HCC患者。对供体和受体的IL6基因中的6个标签单核苷酸多态性进行基因分型。根据HCC复发情况评估人口统计学特征、HCC特征和IL6基因多态性。

结果

移植前乙肝病毒DNA(P = 0.014)、移植前血清甲胎蛋白(P = 0.035)、结节数量(P = 0.011)、主结节直径(P = 0.001)、大血管侵犯(P = 0.001)、微血管侵犯(P = 0.001)、HCC超出米兰标准(P < 0.001)以及供体rs2069852 AA基因型(P = 0.010)与HCC复发相关。供体具有rs2069852 AA基因型的患者的无复发生存率和总生存率显著低于供体具有AG和GG基因型的患者(分别为P = 0.011和P = 0.026)。无复发生存和总生存的独立危险因素为微血管侵犯(P = 0.003;P = 0.002)、HCC超出米兰标准(P < 0.001;P = 0.001)以及供体rs2069852 AA基因型(P = 0.002;P = 0.010)。

结论

我们的数据表明,供体IL6 rs2069852基因多态性可能是汉族人群肝移植后HCC复发的潜在遗传标志物。

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