NET-1蛋白表达水平在肝细胞癌患者预后中的意义

Prognostic Significance of Neuroepithelial Transforming Protein 1 Expression Pattern in Human Hepatocellular Carcinoma

目的:探讨神经上皮转换蛋白1(NET-1)表达水平在肝细胞癌(HCC)患者预后中的意义。方法:采用免疫组织化学染色检测368对HCC和正常肝组织(NLT)样本中NET-1的表达水平。进行Kaplan-Meier生存曲线和Cox回归分析,评估HCC的预后。结果:在368例HCC组织中NET-1表达的阳性率为86.7%(319/368),与Edmondson-Steiner分期(P=0.02)以及TNM阶段(P=0.01)呈正相关。NET-1表达水平与肝内转移(P=0.008)和门静脉侵润(P=0.007)呈正相关。高表达NET-1的HCC病人比具有低表达NET-1或表达缺失NET-1(分别为P=0.001和P=0.002)的病人具有更短的无病存活期或者总存活期。多元Cox回归分析表明NET-1蛋白表达(相对危险性[RR],5.8;P=0.01)对HCC病人是一个独立的预后预测因素。结论:NET-1的表达情况可能成为HCC病人存活期的一个新预测因素。为研究针对NET-1靶点的新的治疗方法提供了理论基础。

Objective：To study the prognostic significance of Neuroepithelial Transforming Protein 1 expression pattern in Human Hepatocellular Carcinoma. Methods：Immunohistochemical staining was used to determine NET-1 expression level in 368 paired HCC and normal liver tissue （NLT） specimens. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of HCC. Results：Among 368 specimens of HCC, the positive rate of NET-1 protein expression in HCC tissues was 86.7% （319/368）, and the increased NET-1 expression was correlated significantly with high Edmondson-Steiner grade （P=0.02） and TNM stage （P=0.01）. The expression level of NET-1 in HCC tissues was associated with intrahepatic metastasis （P=0.008） and portal vein infiltration （P=0.007）. Patients with HCC who had moderate-strong NET-1 positive expression had either poorer disease-free survival or poorer overall survival than patients who had with negative-low positive NET-1 expression （P=0.001 and P=0.002, respectively）. Multivariate Cox regression analysis revealed that NET-1 protein expression （relative risk [RR], 5.8; P=0.01） was an independent prognostic factor for patients with HCC. Conclusion：Taken together, our study suggests for the first time that NET-1 status may be a new predictor of survival for HCC patients and provides the rationale for developing a novel therapy targeting NET-1 against this fatal malignancy.