Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE.
Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE.
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DOI：
10.1016/j.tranon.2015.05.002
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发表时间：
2015-08
影响因子：
5
通讯作者：
Mazzocca A
中科院分区：
文献类型：
--
作者：
Divella R;Daniele A;Abbate I;Savino E;Casamassima P;Sciortino G;Simone G;Gadaleta-Caldarola G;Fazio V;Gadaleta CD;Sabbà C;Mazzocca A
尽管已经提出了几种分子标志物来预测肝细胞癌(HCC)的疾病进展，但预测治疗反应的标志物仍然不能令人满意。在此，我们提出基因多态是肝细胞癌患者接受经导管动脉化疗栓塞术(TACE)治疗后预后不良的潜在预测因素。特别是，我们发现−基因启动子区域675bp的鸟苷插入/缺失多态，即4G/4G，在75例接受肝动脉化疗栓塞术的肝癌患者中预示着不良预后。通过结合EL ISA和SERPINE1启动子的研究，我们发现4G/4G基因型患者血浆纤溶酶原激活物抑制物-1(PAI-1)水平的升高与肝癌患者TACE术后总生存率的降低显著相关。我们的分析提供了证据，证明SERPINE1基因的变异在决定接受TACE治疗的患者的预后中起着作用。除了疾病预后不佳外，4G/4G变异也是化疗反应的不利预测因素。
Although several molecular markers have been proposed as prognostic of disease progression in Hepatocellular carcinoma (HCC), predictive markers of response to treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a potential predictive factor of poor prognosis in HCC patients treated with transcatheter arterial chemoembolization (TACE). In particular, we show that the guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene at the − 675 bp position, named 4G/4G, predicts poor prognosis in a cohort of 75 patients with HCC undergoing TACE. By a combination of ELISA and SERPINE1 promoter study, we found that the presence of elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) in patients with 4G/4G genotype is significantly associated with reduced overall survival compared to patients with 5G/5G or 4G/5G genotype in HCC patients after TACE. Our analysis provided evidence that variation in SERPINE1 gene plays a role in defining the outcome in patients treated with TACE. In addition to a poor disease outcome, the 4G/4G variant represents an unfavorable predictive factor for response to chemotherapy as well.