Donor miR-196a-2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population
Donor miR-196a-2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population
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供体 miR-196a-2 多态性与中国汉族人群肝移植后肝细胞癌复发相关。
DOI：
10.1002/ijc.29821
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发表时间：
2016-02-01
影响因子：
6.4
通讯作者：
Zheng, Shusen
中科院分区：
文献类型：
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作者：
Xu, Xiao;Ling, Qi;Zheng, Shusen
肝细胞癌（HCC）复发是肝移植（LT）后主要死亡原因之一。我们旨在评估供体和受体的单核苷酸多态性（SNP）与肝移植后HCC复发风险之间的关联。本研究共纳入155例因HCC接受初次肝移植的成年患者。对10个与HCC易感性相关的SNP进行基因分型。接受携带rs11614913纯合CC变异供肝的患者，其HCC复发率显著高于接受TT野生型供肝的患者（41.7% 对比15.3%，p = 0.009），且无瘤累积生存率更低（p = 0.005）。供体的rs11614913基因变异是HCC复发的独立危险因素（每个C等位基因的优势比为2，p < 0.05），并且能显著提高临床模型（米兰标准、加州大学旧金山分校标准和杭州标准）的预测能力。携带rs11614913 CC纯合子的供肝，其miR - 196a表达水平高于TT型（p = 0.002）。在小鼠肝脏慢病毒感染及HCC原位小鼠模型中，肝脏miR - 196a过表达组的肿瘤体积显著大于对照组（p = 0.001）。肝脏中肿瘤大小与miR - 196a表达密切相关（r = 0.693，p = 0.001）。综上所述，供体miR - 196a - 2 rs11614913多态性与肝移植后HCC复发相关，并提高了临床模型的预测价值。肝脏中miR - 196a的过表达可能为HCC的发生发展提供了有利的肿瘤微环境。
Recurrence of hepatocellular carcinoma (HCC) is one of the leading causes of death after liver transplantation (LT). We aim to evaluate the association of donor and recipient single nucleotide polymorphisms (SNPs) with the risk of HCC recurrence after LT. A total of 155 adult patients who underwent primary LT for HCC were enrolled. Ten SNPs associated with HCC susceptibility were genotyped. Patients who received donor livers with the rs11614913 homozygous CC variant presented significantly higher recurrence rates of HCC (41.7 vs. 15.3%, p = 0.009) and lower cumulative tumor-free survival (p = 0.005) than those who received TT wild-type donor livers. The donor rs11614913 genetic variant was an independent risk factor for HCC recurrence (odds ratio = 2 per each C allele, p < 0.05) and could significantly improve the predictive abilities of clinical models (Milan, UCSF and Hangzhou criteria). Donor livers homozygous for rs11614913 CC were associated with a higher miR-196a expression than TT (p = 0.002). In a lentiviral infection of mouse liver and orthotopic mouse model of HCC, the liver miR-196a overexpression group showed a significantly larger tumor size than the control group (p = 0.001). There is a close association between the tumor size and expression of miR-196a in the liver (r = 0.693, p = 0.001). In conclusion, the donor miR-196a-2 rs11614913 polymorphism is associated with HCC recurrence after LT and improves the predictive value of clinical models. The overexpression of miR-196a in the liver might provide a tumor-favorable environment for the development of HCC.