肝细胞肝癌中Wnt5a基因的表达及其临床意义

目的 探讨Wnt5a基因mRNA及其蛋白在肝细胞肝癌(hepatocellular carcinoma, HCC)中的表达规律及其临床意义.方法 应用实时定量RT-PCR方法 检测22例HCC癌和癌旁配对组织中Wnt5a基因mRNA表达,采用免疫组织化学(ABC)法检测76例Wnt5a蛋白的表达情况,结合病人的临床病理资料分析Wnt5a基因在HCC中的表达意义.结果 对比癌旁肝组织,68%(15/22)的肝癌组织Wnt5a基因mRNA呈上调表达(P=0.038);而80.3%(61/76)的HCC癌组织Wnt5a蛋白显示低或阴性表达(P<0.001),Wnt5a蛋白低表达与病人的性别、肿瘤的大小、肿瘤的分化程度、HBsAg、以及有无肝硬化无关(P>0.05),而与高的甲胎蛋白水平(AFP,P=0.020)和差的肿瘤分期有关(P<0.001).结论 Wnt5蛋白缺失表达是HCC进展中的频发事件,Wnt5a在HCC肿瘤发生过程中可能发挥肿瘤抑制基因活性,该蛋白极可能是一个有用的HCC预后不良指标.

Expression of Wnt5a gene in human hepatocellular carcinoma and its clinical significance

Objective To study the expression of Wnt5a gene mRNA and protein in human hep-atocellular carcinoma(HCC) and explore its clinical significance. Methods Wnt5a mRNA level was measured in 22 patients with HCC and paired non-tumorous liver tissues by real-time RT-PCR. Immu-nohistochemical staining of Wnt5a was performed in 76 patients with HCC using ABC system. The re-lationship between expression of Wnt5a gene and clinicopathological parameters in patients with HCC was analyzed. Results The Wnt5a was overexpressed in 15 of 22 hepatocellular carcinomas (68%). Wnt5a was highly expressed in hepatocellular carcinoma cells in contrast to its low level of expression in non-neoplastic liver cells(P=0.038). The reduced Wnt-5a protein expression, evident in 80.3% (61/76) of the HCCs, was significantly associated with higher serum AFP level(P=0.020) and poor tumor stage(P<0.001), but was not correlated with sex of patients,size of tumor, HBsAg, hepatic cirrhosis and the differentiation level of tumor(P>0.05). Conclusion The cytoplasmic loss of Wnt-5a protein is a frequent progression event in HCC. Our data support the notion that Wnt-Sa retains tumor suppressor function and may be a useful indicator of poor prognosis in HCC.