Notch1在肝癌组织中的表达情况及其临床意义

Expression and significance of Notch1 in hepatocellular carcinoma

  • 摘要:
    目的 研究Notch1在肝癌组织中的表达情况及其与肝癌临床病理因素和预后的关系。
    方法 收集2005年6月至2008年6月第四军医大学附属西京医院收治的110例肝癌患者手术切除的肝癌组织及相应癌旁组织标本,采用免疫组织化学方法检测其中Notch1表达情况,并分析Notch1表达与肝癌临床病理因素以及患者预后的相关性。Notch1免疫组织化学染色结果与各项临床病理因素之间的关系分析采用X2检验或Fisher确切概率法,Kaplan-Meier法绘制生存曲线,生存情况分析采用Log-rank检验,采用COX回归模型进行单因素及多因素分析。
    结果 在肝癌组织中,Notch1表达呈现不同结果:27.27%(30/110)阴性表达,29.09%(32/110)弱阳性表达,19.09%(21/110)阳性表达,24.55%(27/110)强阳性表达,56.36%(62/110)染色结果为低表达。部分癌旁组织中Notch1染色结果显示为弱阳性表达,其余均为阴性表达,癌旁组织中Notch1均为低表达。肝癌组织中Notch1阳性表达与肿瘤分化程度、卫星灶、门静脉癌栓、淋巴结转移、美国癌症联合委员会(AJCC)分期等因素相关(X2=6.490,8.959,9.068,23.432,22.123,P<0.05)。Notch1高表达患者术后3年平均生存时间为8个月,显著低于Notch1低表达患者的20个月(Log-rank值=35.096,P<0.05)。单因素分析结果表明:Notch1阳性染色、肿瘤分化程度、肿瘤数量、卫星灶、门静脉癌栓、淋巴结转移和AJCC分期与肝癌患者的生存时间相关(RR=3.364,3.402,2.164,8.548,9.470,16.717,6.011,P<0.05)。多因素分析结果表明:Notch1阳性染色、肿瘤分化程度、卫星灶、门静脉癌栓、AJCC分期是肝癌患者独立的生存预测因子(RR=1.883,2.787,3.460,5.254,2.952,P<0.05)。
    结论 癌旁组织中Notch1为低表达,肝癌组织中Notch1表达较癌旁组织明显增高,Notch1可能参与了肝癌的发生、发展,Notch1与肝癌的临床病理因素及预后关系密切,可以作为肝癌的独立预测因子。

     

    Abstract:
    Objective To investigate the expression of Notch1 in hepatocellular carcinoma (HCC) tissues and to evaluate its relationship with clinicopathological features and prognosis of HCC patients.
    Methods A total of 110 samples of HCC tissues and noncancerous adjacent liver tissues were collected from Xijing Hospital of the Fourth Military Medical University from June 2005 to June 2008. The expressions of Notch1 and the relationship between Notch1 expression and the clinicopathological features and prognosis of HCC patients were analyzed using the chisquare test and Fisher exact probability. The survival curve was drawn by Kaplan-Meier method, and the survival was analyzed by using the log-rank test.
    Results Different expressions of Notch1 were detected in HCC tissues. Negative expressions of Notch1 were detected in 30 samples (27.27%), weak positive expressions of Notch1 in 32 samples (29.09%), positive expressions of Notch1 in 21 samples (19.09%), and strong positive expression of Notch1 in 27 samples (24.55%). There were some weak positive stainings of Notch1 in noncancerous adjacent liver tissues, and all the Notch1 expressions in the noncancerous adjacent liver tissues were at a lower level. Positive expression of Notch1 was correlated with the tumor grade, satellite lesions, portal vein tumor thrombus, metastasis and AJCC stages (X2 =6.490, 8.959, 9.068, 23.432, 22.123, P<0.05). The 3year survival time of patients with high Notch1 expressions was 8 months, which was significantly lower than 20 months of patients with low Notch1 expressions (Log-rank value=35.096, P<0.05). The results of univariate analysis showed that positive expressions of Notch1, tumor differentiation, number of tumors, satellite lesions, portal vein tumor thrombosis,lymph node metastasis, AJCC stage were correlated with the survival of hepatic cancer patients (RR=3.364, 3.402, 2.164, 8.548, 9.470, 16.717, 6.011, P<0.05). The results of multivariate analysis showed that positive expression of Notch1, tumor differentiation, satellite lesions, portal vein tumor thrombus, AJCC stage were independent predictors for the survival of HCC patients (RR=1.883, 2.787, 3.460, 5.254, 2.952, P<0.05).
    Conclusions The expression of Notch1 in noncancerous adjacent liver tissues is weak, and the expression of Notch1 in liver tissues is significantly higher than that in noncancerous adjacent liver tissues. Notch1 might be invloved in the development of HCC. The expression of Notch1 has a close relationship JP3with the clinicopathological features and prognosis of HCC, and it may be an independent prognostic predictor of HCC.

     

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