High thymidylate synthase gene expression predicts poor outcome after resection of hepatocellular carcinoma
High thymidylate synthase gene expression predicts poor outcome after resection of hepatocellular carcinoma
复制标题
DOI：
10.1371/journal.pone.0219469
复制
发表时间：
2019-07-10
期刊：
影响因子：
3.7
通讯作者：
Warren, Robert S.
中科院分区：
文献类型：
--
作者：
Donner, David B.;Nakakura, Eric K.;Warren, Robert S.
前言肝细胞癌(肝细胞癌)切除后的预后有很高的变数。与临床病理因素相比，使用分子标记来预测预后还没有得到很好的研究。我们研究了肝细胞癌切除后胸苷合成酶(TS)基因表达和基因多态性对预后的意义。检测肝细胞癌组织中TS基因的表达水平和基因多态性。采用Kaplan-Meier曲线和Cox比例风险模型对预后因素进行评估。在单因素分析中，对生存率有负面影响的变量包括TNM分期、微血管侵犯和TS高表达。TS高表达组的中位生存期为54个月，5年精算生存率为47%。TS低表达组未达到中位生存期，5年精算生存率为91%。在多因素分析中，仅TS高表达仍是预后不良的独立预测因素(HR=10.77，95%CI 1.36~84.91；P=0.02)。TS基因多态性与TS表达或总生存期无关。结论TS高表达预示着肝细胞癌切除后预后不良。分子标志物可能是预测肝细胞癌切除术后患者预后的可靠指标。
IntroductionPrognosis after resection of hepatocellular carcinoma (HCC) is highly variable. Compared to clinicopathologic factors, the use of molecular markers to predict outcome has not been well studied. We investigated the prognostic importance of thymidylate synthase (TS) gene expression and polymorphisms in patients after resection of HCC.MethodsPatients who underwent complete resection of HCC for whom tissue was available were identified. TS gene expression level and polymorphisms were determined in HCC specimens. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazard models.ResultsThe study included 67 patients. In univariate analysis, variables that negatively influenced survival included TNM stage, microvascular invasion, and high TS expression. For the high TS expression group, median survival was 54 months and 5-year actuarial survival was 47%. For the low TS expression group, median survival was not reached and the 5-year actuarial survival was 91%. In multivariate analysis, only high TS expression remained an independent predictor of poor survival (HR = 10.77, 95% CI 1.36-84.91; P = 0.02). TS gene polymorphisms were not associated with TS expression or overall survival.ConclusionsHigh TS expression predicts poor outcome after resection of HCC. Molecular markers might be robust predictors of patient outcome after resection of HCC.