论文部分内容阅读
目的探讨gp78蛋白与肝癌组织中的肿瘤转移抑制基因KAI1蛋白可能存在的相互关系。方法收集肝癌组织30例及与其相对应的癌旁组织标本30例。用MHCC-97肝癌细胞接种裸鼠肝脏,产生肝脏原位肿瘤9例及肿瘤转移灶14例,收集肿瘤组织和正常肝脏组织。采用免疫组织化学和蛋白质印迹技术检测相关组织中gp78蛋白及KAI1蛋白的表达。结果蛋白质印迹结果表明,人肝癌组织中gp78蛋白的表达水平(0.350±0.143)明显高于人癌旁组织(0.036±0.003,P=0.016),而KAI1蛋白的表达水平(0.036±0.008)则明显低于人癌旁组织(1.173±0.124,P=0.003)。与癌旁组织相比,30例肝癌组织中24例(80%)gp78水平升高,20例(66.7%)KAI1水平降低;9例裸鼠肝癌组织中8例(88.9%)gp78水平升高,6例(66.7%)KAI1水平降低;14例肝癌转移灶样本中,12例(85.7%)gp78水平升高,13例(92.8%)KAI1水平降低。免疫组织化学结果显示,30例人肝癌组织中,有22例(73.3%)gp78呈强阳性表达(分值≥5分),19例(63.3%)KAI1阳性表达较低(分值≤2分);9例裸鼠原位肝癌组织gp78阳性表达率均较高(分值≥5分),有7例(77.8%)KAI1阳性表达率较低(分值≤1分);14例裸鼠肝癌转移灶中,有12例(85.7%)gp78阳性率表达增高,11例(78.6%)则表现为KAI1表达降低。结论gp78蛋白和肿瘤转移抑制基因KAI1蛋白在肝癌的发生发展,尤其是肝癌的转移过程中发挥了重要作用。与正常肝癌组织相比,原位肝癌和肝癌转移灶的gp78表达水平升高,而KAI1表达水平降低。gp78的过表达导致肿瘤转移抑制因子KAI1表达水平降低,可能是肝癌转移浸润的机制之一。
Objective To investigate the possible relationship between gp78 protein and tumor suppressor gene KAI1 in hepatocellular carcinoma. Methods Totally 30 cases of hepatocellular carcinoma and 30 cases of paracancerous tissues were collected. Inoculation of the liver of nude mice with MHCC-97 hepatoma cells resulted in 9 cases of liver tumor in situ and 14 cases of tumor metastasis, collecting the tumor tissue and normal liver tissue. Immunohistochemistry and Western blotting were used to detect the expression of gp78 protein and KAI1 protein in related tissues. Results The results of Western blotting showed that the expression of gp78 protein in human hepatocellular carcinoma was significantly higher than that in human adjacent tissues (0.036 ± 0.003, P = 0.016), while the expression level of KAI1 protein (0.036 ± 0.008) was significantly higher Lower than that in human para-carcinoma (1.173 ± 0.124, P = 0.003). Compared with the adjacent non-cancerous tissues, gp78 levels increased in 24 (80%) of 30 HCC tissues and KAI1 level decreased in 20 (66.7%) HCC tissues. The level of gp78 in 8 (88.9%) of 9 HCC tissues increased , 6 cases (66.7%) KAI1 levels decreased; 14 cases of liver cancer metastasis samples, 12 cases (85.7%) gp78 levels increased, 13 cases (92.8%) KAI1 levels decreased. Immunohistochemistry showed that gp78 was strongly expressed in 22 (73.3%) of 30 human hepatocellular carcinoma tissues (score ≥5), while KAI1 was negative in 19 (63.3%) patients (score ≤2 ). The positive expression rates of gp78 in 9 HCC tissues of nude mice were higher (score≥5), and the expression rate of KAI1 was lower (score≤1) in 7 (77.8%) nude mice. 14 nude mice In liver cancer metastasis, gp78 positive rate was increased in 12 (85.7%) and decreased in 11 (78.6%) patients. Conclusion The gp78 protein and KAI1 protein, an inhibitor of tumor metastasis, play an important role in the development of liver cancer, especially in the metastasis of liver cancer. Compared with normal liver cancer tissues, the expression of gp78 in situ hepatocellular carcinoma and liver cancer metastasis increased, while the expression of KAI1 decreased. Overexpression of gp78 results in decreased expression of KAI1, which may be one of the mechanisms of metastasis and invasion of liver cancer.