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目的探讨Raf激酶抑制蛋白(Raf kinase inhibitor protein,RKIP)在肝癌中的表达及其临床意义。方法采用RT-PCR方法检测肝细胞癌、癌旁组织及正常肝组织中RKIP mRNA的表达;采用组织芯片的免疫组织化学方法检测RKIP蛋白和磷酸化的RKIP蛋白的表达,并分析RKIP蛋白和磷酸化的RKIP的表达与肝细胞癌临床病理学特征的关系。结果RKIP mRNA在肝细胞癌组织、癌旁肝组织及正常肝组织的表达差异无统计学意义(P>0.05)。肝细胞癌、癌旁肝组织及正常肝组织中RKIP蛋白表达的阳性率分别为22.2%、86%、93.8%,磷酸化的RKIP蛋白表达的阳性率分别为29.2%、84%、93.8%;肝癌组织中RKIP和磷酸化的RKIP蛋白表达均显著低于癌旁及正常肝组织(P<0.05);RKIP和磷酸化的RKIP蛋白表达与肿瘤大小、AFP水平及有无门静脉或胆管癌栓无关(P>0.05);RKIP和磷酸化的RKIP蛋白表达与肝细胞癌分化程度及有无肝内或淋巴转移有关,中高分化组RKIP和磷酸化的RKIP蛋白表达高于低分化组,无肝内或淋巴转移组高于有肝内或淋巴转移组(P<0.05)。结论RKIP和磷酸化的RKIP蛋白表达的减少或缺失与肝癌的发生、发展、侵袭转移密切相关。
Objective To investigate the expression of Raf kinase inhibitor protein (RKIP) in hepatocellular carcinoma (HCC) and its clinical significance. Methods RT-PCR was used to detect the expression of RKIP mRNA in hepatocellular carcinoma, para-cancerous tissue and normal liver tissue. The expression of RKIP protein and phosphorylated RKIP protein was detected by immunohistochemistry with tissue microarray. The relationship between the expression of RKIP and the clinicopathological features of hepatocellular carcinoma. Results There was no significant difference in the expression of RKIP mRNA between hepatocellular carcinoma tissues, adjacent liver tissues and normal liver tissues (P> 0.05). The positive rates of RKIP protein expression in hepatocellular carcinoma, adjacent liver tissue and normal liver tissue were 22.2%, 86% and 93.8%, respectively. The positive rates of RKIP protein expression were 29.2%, 84% and 93.8% respectively. The expressions of RKIP and phospho-RKIP in hepatocellular carcinoma tissues were significantly lower than those in para-cancerous tissues and normal liver tissues (P <0.05). The expressions of RKIP and phospho-RKIP were not associated with tumor size, AFP level and portal vein or cholangiocarcinoma P> 0.05). The expression of RKIP and phosphorylated RKIP protein were correlated with the degree of hepatocellular carcinoma differentiation and the intrahepatic or lymphatic metastasis. The expressions of RKIP and phosphorylated RKIP protein in well-differentiated group were higher than those in poorly differentiated group The lymphatic metastasis group was higher than the intrahepatic or lymphatic metastasis group (P <0.05). Conclusion The decrease or loss of RKIP and phosphorylated RKIP protein expression is closely related to the occurrence, development, invasion and metastasis of HCC.