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Akt2和Beclin 1在原发性肝癌中的表达及临床意义
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摘要
目的:通过检测Akt2和Beclin 1在原发性肝癌、肝硬化和正常肝脏组织的表达水平,结合一些临床病理指标,探讨Akt2和Beclin 1的表达水平在原发性肝癌发生发展及转移中的作用及其相互关系。
     方法:用RT-PCR和免疫组织化学Elivision法检测76例原发性肝癌组织、54例肝硬化组织和20例正常肝脏组织中的Akt2和Beclin 1的表达水平,结合临床病理指标及其相关性,进行统计学分析。
     结果:(1)Akt2主要在肝癌、肝硬化组织中表达,在正常组织中低表达。RT-PCR技术检测76个肝癌组织、54个肝硬化组织,20个正常肝脏组织标本中Akt2 mRNA表达水平。UVIsoft测得肝癌组织、肝硬化组织、正常肝脏组织中Akt2与GAPDH相对灰度值比分别为0.90±0.14、0.19±0.05、0.02±0.02,其差异有统计学意义(F=3.069,P<0.05)。通过免疫组织化学的方法检测Akt2蛋白表达在76例肝癌中阳性率为90.79% (69/76),54例肝硬化组织中阳性率为25.92%(14/54),20例正常肝组织中阳性率为5%(1/20),肝癌组、肝硬化组和正常肝组织组中Akt2表达差异有统计学意义(χ2=82.881,P<0.05)。Akt2的表达与年龄、性别、肿瘤分级、肿瘤大小、HBSAg、AFP值无关(P>0.05),但与肝硬化程度及有无门静脉或胆管癌栓有关(P<0.05)。
     (2)Beclin 1主要在肝癌、肝硬化组织中表达,在正常组织中低表达。RT-PCR技术检测76个肝癌组织、54个肝硬化组织,20个正常肝脏组织标本中Beclin 1 mRNA表达水平。UVIsoft测得肝癌组织、肝硬化组织,正常肝脏组织中Beclin 1与GAPDH相对灰度值比分别为0.78±0.10、0.39±0.04、0.04±0.02,其差异有统计学意义(F=5.78,P<0.05)。免疫组织化学的方法检测Beclin 1蛋白表达在76例肝癌中阳性率为84.21% (64/76),54例肝硬化组织中阳性率为37.04%(20/54),20例正常肝组织中阳性率为10%(2/20),肝癌组、肝硬化组和正常肝组织组中Akt2表达差异有统计学意义(χ2=49.85,P<0.05)。原发性肝癌中Beclin 1的表达与年龄、性别、肿瘤分级、肿瘤大小、HBSAg、AFP值及肝硬化程度无关(P>0.05),但与有无门静脉或胆管癌栓有关(P<0.05)。
     (3)原发性肝癌中Akt2与Beclin 1成正相关(r=0.947,P=0.04)。
     结论:Akt2和Beclin 1在原发性肝癌中高表达,两者相互作用且共同参与原发性肝癌的发生、发展过程,联合检测Akt2和Beclin 1对判断其发生和转移有重要价值,是有潜力的肝癌治疗的候选靶基因。
Objective: To detect Akt2 and Beclin 1 expression in primary hepatic carcinoma (PHC), cirrhotic liver and normal liver tissues, and study their correlations to the clinic pathological features. To explore the effect of Akt2 and Beclin 1 expression in the occurrence,development and metastasis of primary hepatic carcinoma and their interrelation.
     Method: The expression of Akt2 and Beclin 1 in 76 cases of primary hepatic carcinoma tissue,54 cases of cirrhotic liver tissue and 20 cases of normal liver tissues were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Elivision immunohistochemistry. The condition of the clinical pathological parameters and their interrelation were analyzed using statistical method.
     Result:
     1. Akt2 was mainly expressed in primary hepatic carcinoma and cirrhotic liver tissues, there was low expression in normal liver tissues. The Akt2 mRNA expression were 0.90±0.14,0.19±0.05,0.02±0.02 in PHC tissues,cirrhotic liver tissues and normal liver tissues, the difference was statistically significant(F=3.069,P<0.05); The Akt2 protein expression were 90.79%,25.92%, 5% in PHC tissues,cirrhotic liver tissues and normal liver tissues, the difference was statistically significant(χ2=82.881,P<0.05). The expression of Akt2 showed no obvious correlations with the age, gender, Edmondson-steiner grade, tumor size, HBSAg and AFP (P>0.05),but was related to portal vein tumor thrombi and biliary tumor thrombi and the degree of hepatic cirrhosis (P<0.05).
     2. Beclin 1 was also mainly expressed in primary hepatic carcinoma and cirrhotic liver tissues and there was low expression in normal liver tissues. The Beclin 1 mRNA expression were 0.78±0.10,0.39±0.04,0.04±0.02 in PHC tissues、cirrhotic liver tissues and normal liver tissues, the difference was statistically significant(F=5.78,P<0.05); The Akt2 protein expression were 84.21%,37.04%,10% in PHC tissues、cirrhotic liver tissues and normal liver tissues, the difference was statistically significant(χ2=49.85, P<0.05). The expression of Beclin 1 showed no obvious correlations with the age, gender, Edmondson-steiner grade, tumor size, HBSAg, AFP and the degree of hepatic cirrhosis (P>0.05),but was related to portal vein tumor thrombi and biliary tumor thrombi (P<0.05).
     3. The expression rate of Akt2 was significantly correlated with that of Beclin 1 in primary hepatic carcinoma(r=0.947,P=0.04).
     Conclusion: There were higher expression of Akt2 and Beclin 1 in primary hepatic carcinoma. Akt2 and Beclin 1 interact one another and participate in the occurrence、development and metastasis of PHC. Combined detection of Akt2 and Beclin 1 has important value for prediction of occurrence and metastasis. They are both potential target gene for the therapy of PHC.
引文
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