肝癌组织中Raf激酶抑制蛋白和磷酸化Raf激酶抑制蛋白的表达及其意义

Expression and Significance of Raf Kinase Inhibitor Protein and Phosphorylated Raf Kinase Inhibitor Protein in Hepatocellular Carcinoma

目的探讨Raf激酶抑制蛋白(Raf kinase inhibitor protein,RKIP)和磷酸化Raf激酶抑制蛋白(Phosphorylated raf kinase inhibitor protein,P-RKIP)在肝细胞癌中的表达及其临床意义。方法应用组织芯片和免疫组织化学方法检测RKIP蛋白和磷酸化的RKIP蛋白在72例肝细胞癌组织、50例癌旁肝组织及16例正常肝组织中的表达,并分析RKIP的表达与肝细胞癌临床病理学特征的关系。采用Western blot方法检测36例肝细胞癌、36例癌旁组织及12例正常肝组织中RKIP蛋白和磷酸化的RKIP蛋白的表达。结果免疫组化结果显示肝细胞癌、癌旁及正常肝组织中RKIP的阳性率分别为22.2%、86%、93.8%,P-RKIP为29.2%、84%、93.8%;肝癌组织中RKIP和P-RKIP的表达显著低于癌旁及正常肝组织,差异有统计学意义(P<0.05),而且肝癌组织和癌旁肝组织中两者蛋白的表达均呈显著正相关(P=0.000,P=0.005);RKIP和P-RKIP的表达均与肝癌有无肝内或淋巴结转移及分化程度有关(P<0.05)。Western blot结果显示肝癌组织中RKIP和P-RKIP的表达显著低于癌旁及正常肝组织。结论RKIP和P-RKIP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） and P-RKIP in hepatocellular carcinoma （HCC） and their relation with the＇invasion and metastasis of HCC. Methods Immunohis-tochemistry and western-blot was used to detect the expression of RKIP and P-RKIP in HCCs, paratumor tissues and normal liver tissues. Statistical analysis was used to determine the relationship between their expression and clinicopathological parameters. Results Statistical analysis revealed that the expression level of RKIP and P- RKIP in tumor tissue were significantly lower than that in tumor-surrounding tissue and in normal liver tissue（P 〈0. 05）. RKIP and P-RKIP expression are dramatically lower in HCC; with intrahepatic or lymphatic metastasis than that in without respectively. In moderately and well differentiated HCC both RKIP and P-RKIP positive stain rate is significantly higher than that in poorly differentiated HCC. There was a positive correlation between RKIP and P-RKIP expression in HCCs（P = 0. 000） and in paratumor tissues（P = 0. 005）. Conclusion Our findings indicate that down-regulation of RKIP and P-RKIP expression may serve as a risk marker for HCC development, progression and metastasis.