Wang Pusen, Song Weiyong, Li Hao, Wang Cunguang, Shi Baojie, Guo Wenzhi, Zhong Lin
Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
Department of General Surgery, The First People's Hospital of Yongkang City, Yongkang City, Zhejiang Province, 321300, China.
Tumour Biol. 2015 Sep;36(10):7807-15. doi: 10.1007/s13277-015-3370-x. Epub 2015 May 6.
Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) is potential cause for the poor outcome. Smoothened (SMO) gene has been considered associating with HCC and HCC recurrence, but its association with HCC recurrence after OLT is not clear yet. In this study, we aim at evaluating the association between donor and recipient SMO gene polymorphisms and HCC recurrence after OLT. A total of 76 patients with HCC who had undergone OLT from July 2007 to August 2012 were included. A single nucleotide polymorphism (SNP), SMO rs3824, located at the 3'UTR region, was genotyped and analyzed in both donor and recipient. We demonstrated that recipient rs3824 polymorphism was significantly associated with HCC recurrence following OLT. In multivariate logistic regression analysis, TNM stage (p = 0.001), recipient SMO rs3824 genotype (CG vs. CC/GG p = 0.001), and histologic grade (p = 0.019) were identified as independent risk factors of HCC recurrence. Recurrence-free survival (RFS) and overall survival (OS) were significantly higher in the recipient CC/GG group than in the CG group (p = 0.003 and p = 0.011, respectively). Cox proportional hazards modeling revealed that TNM stage, recipient SMO rs3824 genotype, pre-OLT serum AFP level, and histologic grade were independent factors (p < 0.05) for patients' clinical outcomes. In conclusion, recipient SMO rs3824 polymorphism is associated with an increased risk of HCC recurrence following OLT and has a potential clinical value for the prognosis of HCC patients treated with OLT.
原位肝移植（OLT）后肝细胞癌（HCC）复发是导致预后不良的潜在原因。平滑肌瘤（SMO）基因被认为与HCC及HCC复发有关，但其与OLT后HCC复发的关联尚不清楚。在本研究中，我们旨在评估供体和受体SMO基因多态性与OLT后HCC复发之间的关联。纳入了2007年7月至2012年8月期间接受OLT的76例HCC患者。对位于3'UTR区域的单核苷酸多态性（SNP）SMO rs3824在供体和受体中进行基因分型和分析。我们证明受体rs3824多态性与OLT后HCC复发显著相关。在多因素逻辑回归分析中，TNM分期（p = 0.001）、受体SMO rs3824基因型（CG与CC/GG相比，p = 0.001）和组织学分级（p = 0.019）被确定为HCC复发的独立危险因素。受体CC/GG组的无复发生存期（RFS）和总生存期（OS）显著高于CG组（分别为p = 0.003和p = 0.011）。Cox比例风险模型显示，TNM分期、受体SMO rs3824基因型、OLT前血清甲胎蛋白水平和组织学分级是影响患者临床结局的独立因素（p < 0.05）。总之，受体SMO rs3824多态性与OLT后HCC复发风险增加有关，对接受OLT治疗的HCC患者的预后具有潜在临床价值。
