多药耐药相关蛋白基因在原发性肝细胞癌中的表达及意义

目的 研究多药耐药相关蛋白(MRP)基因mrp在肝细胞癌(HCC)中的表达水平与其化疗疗效及甲胎蛋白(AFP)的关系。 方法采用SP免疫组织化学方法和聚合酶链反应技术对54例术前未化疗的未能切除的HCC、24例癌旁肝组织及12例肝炎后肝硬化组织中mrp编码的MRP和mRNA mrp的表达进行检测。术后所有病人常规化疗,分析mrp表达与HCC化疗疗效关系。并对其AFP阳性的38例HCC病人术后化疗,分析mrp表达与AFP变化的关系。 结果 MRP和mRNA mrp在3种组织中的mrp表达率分别为61.1％、25.0％、33.3％和77.8％、37.5％、41.7％; HCC组织中mrp表达显著高于其他组织中的mrp表达(x2=9.842,P<0.01;x2=13.956,P<0.01)。MRP及mRNA mrp阴性和阳性组HCC的化疗有效率分别为61.9％、30.3％和75.0％、33.3％,两组疗效差异有显著性(x2=5.242.P<0.05; x2=6.627,P<0.05);两组AFP有效率分别为62.5％、27.3％和87.5％、30.0％,mrp表达阴性组显著高于阳性组(x2=4.710,P<0.05;x2=8.566,P<0.01)。 结论 HCC多药耐药和mrp表达有关,HCC耐药起源于内源性多药耐药。检测mrp表达对肝癌的化疗耐药具有重要的指导意义;mrp表达可作为预测HCC化疗敏感性的参考指标。

Expression and implication of multidrug resistance associated -protein gene in primary hepatocellular carcinoma

Objective To investigate the relationship between the expression of mrp and both the responses to chemotherapy and the level of a -fetoprotein (AFP). Methods S-P immunohistochemical staining and in situ PCR were adopted to detect MRP and mRNA mrp in 54 cancer tissuses taken from untreated HCC patients whose tumor could not be removed during the operation, 24 para-cancer tissues, and 12 posthepatitis cirrhosis paraffin-embedded tissues. The relationship between the expression of mrp and their curative effect to chemotherapy in all the patients was analyzed, so was the relationship between the expression of mrp and the level of AFP in 38 patients whose AFP was positive after operation. Results The positive rates of expressing MRP and mRNA mrp in the three kinds of tissues were 61.1%, 25.0%, 33.3% and 77.8%, 37.5%, 41.7%, respectively, with higher rates in HCC tissues than those in other tissues ( x2 = 9.842, P < 0.01; x2 = 13.956, P < 0.01). The rates of curative effect to chemotherapy in groups of negative and positive MRP and mRNA mrp expression were 61.9%, 30.3% and 75.0%, 33.3%, respectively, with significant difference between the negative and positive groups (x2= 5.242, P < 0.05; x2 = 6.627, P < 0.05). As the same as the percentage of curative effect to chemotherapy, the rates of AFP level decreased evidently were 62.5%, 27.3% and 87.5%, 30.0%, with remarkable difference between the two groups ( x2= 4.710, P < 0.05; x2= 8.566, P < 0.05). Conclusions The multidrug resistance (MDR) of HCC is related to mrp expression, which initiates the intrinsic MDR. There is an important significance by detecting mrp expression in selecting chemotherapeutic method, and the expression of mrp can act as an indicator for chemotherapeutic sensitivity in HCC patients.