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广西三地人群肝组织中修复蛋白hOGG1和MGMT的表达

发布时间:2018-12-26 15:21
【摘要】:目的:通过比较广西南宁,柳州,桂林三地人群肝癌组织和正常肝组织中hOGG1修复蛋白和MGMT修复蛋白的表达水平,了解三地人群肝组织中DNA损伤的修复情况及其AFB1暴露的关系。 材料和方法:收集南宁,柳州,桂林三地病理蜡块切片共428例,其中南宁地区HCC组103例,正常对照组58例;柳州地区HCC组89例,正常对照组55例;桂林地区HCC组86例,正常对照组37例。通过免疫组织化学(Immunohistochemistry, IHC)法检测hOGG1蛋白,MGMT修复蛋白表达水平及AFB1-DNA加合物水平的表达情况。 结果:三地HCC组的hOGG1蛋白表达水平和平均光密度值均高于正常对照组(P0.05)。三地HCC组中,南宁HCC组表达水平和平均光密度值最高(P0.05)。三地正常对照组的hOGG1蛋白表达水平和平均光密度值也存在差异(P0.05),南宁正常对照组表达水平和平均光密度值最高,桂林正常对照组表达水平和平均光密度值最低;三地HCC组的MGMT蛋白表达水平和平均光密度值均低于正常对照组(P0.05);三地HCC组的MGMT蛋白表达水平和平均光密度值无显著差异(P0.05),三地正常对照组的MGMT蛋白表达水平和平均光密度值无显著差异(P0.05);南宁HCC组AFB1-DNA加合物阳性表达水平和平均光密度高于癌旁组(P0.05)和正常对照组(P0.05),柳州HCC组AFB1-DNA加合物阳性表达水平和平均光密度高于正常对照组(P0.05),桂林地区AFB1-DNA加合物阳性表达水平和平均光密度与正常对照组无差异(P0.05)。三地HCC组中,南宁组表达水平和平均光密度最高(P0.05),桂林组表达水平和平均光密度最低。三地正常对照组阳性表达水平无明显差异(P0.05)。hOGG1修复蛋白表达与AFB1-DNA加合物表达在南宁地区的HCC组、癌旁组和正常对照组的均存在相关性,而在柳州和桂林地区各组中未发现有明显相关性。MGMT修复蛋白表达与AFB1-DNA加合物表达在三地各组中均未发现有明显相关性。 结论:三地肝癌人群中肝细胞DNA氧化损伤修复水平存在差异,MGMT修复蛋白表达缺失造成DNA损伤修复功能下降可能在肝癌的发生过程中起到重要作用。广西AFB1暴露水平存在区域性分布差异,南宁地区AFB1暴露水平要高于以桂林地区。AFB1暴露是HCC高发的危险因素。同时在较高的AFB1暴露水平下,氧化损伤修复蛋白hOGG1表达与AFB1-DNA加合物表达呈现相关性相关,严重的DNA氧化损伤可能为AFB1致肝癌的重要原因之一。
[Abstract]:Objective: to compare the expression levels of hOGG1 repair protein and MGMT repair protein in liver cancer tissues and normal liver tissues in Nanning, Liuzhou and Guilin, Guangxi, and to understand the repair of DNA damage and the relationship between AFB1 exposure and DNA repair in the liver tissues of the three populations. Materials and methods: a total of 428 cases of paraffin sections in Nanning, Liuzhou and Guilin were collected, including 103 cases in HCC group and 58 cases in normal control group in Nanning, 89 cases in HCC group and 55 cases in normal control group in Liuzhou area. There were 86 cases in HCC group and 37 cases in normal control group in Guilin area. The expression of hOGG1 protein, MGMT repair protein and AFB1-DNA adduct were detected by immunohistochemical (Immunohistochemistry, IHC) method. Results: the expression of hOGG1 protein and the average optical density in HCC group were higher than those in normal control group (P0.05). Among the three HCC groups, Nanning HCC group had the highest expression level and average optical density (P0.05). The expression level and average optical density of hOGG1 protein in normal control group were the highest in Nanning control group and the lowest in Guilin normal control group. The expression level and average optical density of MGMT protein in HCC group were lower than those in normal control group (P0.05). There was no significant difference in the expression level and average optical density of MGMT protein in the three HCC groups (P0.05), but there was no significant difference in the MGMT protein expression level and the average optical density value in the normal control group (P0.05). The positive expression level and average optical density of AFB1-DNA adducts in Nanning HCC group were higher than those in paracancerous group (P0.05) and normal control group (P0.05). The positive expression level and average optical density of AFB1-DNA adduct in Liuzhou HCC group were higher than those in normal control group (P0.05), but the positive expression level and average optical density of AFB1-DNA adduct in Guilin area had no difference from those in normal control group (P0.05). Among the three HCC groups, Nanning group had the highest expression level and average optical density (P0.05), and Guilin group had the lowest expression level and mean optical density. The expression of hOGG1 repair protein was correlated with the expression of AFB1-DNA adducts in HCC group, paracancerous group and normal control group in Nanning area. There was no significant correlation between the expression of MGMT repair protein and the expression of AFB1-DNA adduct in Liuzhou and Guilin. Conclusion: there are differences in the repair level of DNA oxidative damage in hepatoma cells in the three regions. The decrease of DNA damage and repair function caused by the loss of MGMT repair protein may play an important role in the pathogenesis of HCC. There were regional distribution differences in AFB1 exposure level in Guangxi, and the AFB1 exposure level in Nanning was higher than that in Guilin. AFB1 exposure was the risk factor of high incidence of HCC. At the same time, the expression of oxidative damage repair protein (hOGG1) was correlated with the expression of AFB1-DNA adducts at high AFB1 exposure level. Severe DNA oxidative damage may be one of the important causes of AFB1 induced liver cancer.
【学位授予单位】:广西医科大学
【学位级别】:硕士
【学位授予年份】:2011
【分类号】:R329

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