【作者】 孙江华；

【导师】 章宗籍； 申丽娟；

【作者基本信息】 昆明医学院 ， 病理学与病理生理学， 2006， 硕士

【摘要】 目的：研究p57^kip2基因在人体肝细胞癌（hepatocellular carcinoma，HCC）不同阶段的杂合性缺失（loss of heterozygosity，LOH）及其mRNA和蛋白表达情况，以及三者之间的关系，以探讨HCC发生的分子生物学机制。方法：运用PCR—聚丙烯酰胺凝胶电泳—银染法对30例肝癌组织p57^kip2基因位点上2个微卫星位点（TH01和D11S2359）进行LOH的检测，同时运用原位分子杂交和免疫组化技术分别检测30例正常肝组织、30例癌周肝硬化和30例肝癌组织中p57^kip2mRNA及P57^kip2蛋白的表达情况。结果：1．LOH：30例肝癌组织中有9例至少在1个微卫星位点（30.0％）表现出LOH，其中分化好肝癌组织和分化差肝癌组织的LOH率之间差异有统计学意义，相关分析呈正相关。2．p57^kip2 mRNA表达：正常肝组织组未见表达，癌周肝硬化组与肝癌组阳性表达率分别为33.33％和16.67％。肝癌组分化好和分化差阳性表达率之间差异有统计学意义，相关分析呈正相关。3．P57^kip2蛋白表达：正常肝组织组未见表达；癌周肝硬化组与肝癌组阳性表达率分别为56.67％和63.33％。肝癌组分化好者与分化差者阳性表达率之间差异有统计学意义，相关分析呈正相关。4．肝癌p57^kip2 LOH与其mRNA表达之间的关系：TH01的LOH与其mRNA表达的缺失有正相关关系；D11S2359的LOH则与其mRNA表达的缺失无相关性；两个位点LOH与mRNA表达之间无相关性。5．肝癌p57^kip2 LOH与蛋白表达之间的关系：单个位点LOH与蛋白表达的缺失都有正相关关系；两个位点同时LOH与蛋白表达的缺失无相关性。6．肝癌p57^kip2mRNA与蛋白表达之间的关系：两者之间无相关性。结论：1．p57^kip2更多还原

【Abstract】 Objective: To study the loss of heterozygosity （LOH） of p57^kip2 and expressions of p57^kip2 mRNA & protein in various stages of human hepatocellular carcinoma （HCC） in order to explore the molecular mechanism of hepatocarcinoma.Methods: LOH of two microsatellite loci （TH01 and D11S2359） were detected in the p57^kip2 gene site by using PCR-polyacrylamide gel electrophoresis-silver staining method. Immunohistochemistry staining and in situ hybirdization （ISH） were also used to show the expression of p57^kip2 mRNA and protein in normal liver tissue, pericancerous cirrhosis and HCC.Results: 1. LOH: LOH was identifided at least in 9 cases out of 30 （30.0%） on one microsatellite loci. The positive rates of LOH in high differentiated HCC tissues and low differentiated HCC tissues were 3.33% and 26.67% respectively, there was significant difference and positive correlation between them. 2.Expression of p57^kip2 mRNA: There were no expressions in normal liver tissue. Expressions in pericancerous cirrhosis and hepatocellular carcinoma were 33.33% and 16.67% respectively. In group of hepatocellular carcinoma tissues, the expressions in high differentiated HCC tissues and low differentiated HCC tissues were 28.57% and 0 respectively, there was significant difference and positive correlation between them.更多还原