肝细胞肝癌组织中Beclin-1与Caspase-9、p53的表达及其意义

发布时间：2018-06-15 15:24

本文选题：肝细胞肝癌 + Beclin-1　；参考：《青岛大学》2017年硕士论文

【摘要】：目的探讨自噬相关蛋白Beclin-1和凋亡蛋白Caspase-9以及p53在肝细胞肝癌(HCC)组织中的表达及其意义,结合临床病理资料分析Beclin-1、Caspase-9及p53在HCC发生发展过程中的作用及三者之间的相关关系,并对患者进行预后分析,为HCC的早期检测、治疗及预后提供更为有效的依据。方法收集HBV病毒相关HCC石蜡标本108例、肝硬化石蜡标本30例及正常肝组织石蜡标本20例,采用免疫组织化学染色方法分别检测三组标本中Beclin-1及Caspase-9、p53的表达情况并分析它们与HCC临床病理参数及患者五年生存时间及无瘤生存时间之间的关系。结果Beclin-1在HCC组中的阳性表达率明显低于正常肝组织组,差异有统计学意义(χ2=5.575,P=0.016),肝硬化组和正常肝组织组,肝硬化组和HCC组的阳性表达率均无统计学差异(χ2=3.704,P=0.054;χ2=0.054,P=0.815);p53在HCC组中的阳性表达率高于正常肝组织组和肝硬化组,差异有统计学意义(χ2=17.297,P=0.000;χ2=21.330,P=0.000);Caspase-9在HCC中的表达明显高于正常肝脏组织(χ2=4.349,P=0.037),而在肝硬化组织与正常肝脏组织及肝硬化组织与HCC组织之间,其表达无显著差异(χ2=0.347,P=0.556;χ2=2.713,P=0.100)。Beclin-1在HCC中的表达与Edmondson病理分级(P=0.010)及AFP的高低(P=0.047)有关,与患者的年龄、性别、肿瘤的大小、数目以及是否有卫星灶、血管癌栓、肝硬化、被膜侵犯、TNM分期均无关(P0.05);p53在HCC中的表达与Edmondson病理分级有关(P=0.001),与患者的年龄、性别、肿瘤的大小、数目、AFP的高低以及是否有卫星灶、血管癌栓、肝硬化、被膜侵犯、TNM分期均无关(P0.05);Caspase-9在HCC中的表达与Edmondson病理分级(P=0.001)及肿瘤是否有卫星灶(P=0.005)密切相关,与患者的年龄、性别、AFP的高低以及肿瘤的大小、数目、是否有血管癌栓、肝硬化、被膜侵犯、TNM分期无关。HCC组织中Beclin-1与p53的表达呈负相关(r=-0241,P=0.012),Beclin-1与Caspase-9的表达呈正相关(r=0.223,P=0.020),Caspase-9与p53在HCC中的表达不相关,没有统计学差异(χ2=5.775,P=0.077)。预后分析Beclin-1、p53及Caspase-9对患者预后的影响,发现其与患者预后有关。Beclin-1高表达的病例其生存时间及无瘤生存时间均长于低表达的病例(P=0.001,P=0.006),Caspase-9阳性表达的病例其生存时间及无瘤生存时间均长于阴性表达的病例(P=0.025);p53阴性表达的病例,生存时间要长于阳性表达的病例(P=0.025),但对于无瘤生存时间没有显著差异(P=0.084)。结论在肝细胞肝癌组织中Beclin-1低表达,Caspase-9与p53均高表达,Beclin-1与p53的表达呈负相关,与Caspase-9的表达呈正相关。Beclin-1及p53可能与HCC的发生有关,Caspase-9可能与HCC的发生及发展均有关。Beclin-1、p53及Caspase-9可作为判断肝细胞肝癌生物学行为及预后的重要指标。
[Abstract]:Objective to investigate the expression and significance of the autophagy associated protein Beclin-1, apoptosis protein Caspase-9 and p53 in hepatocellular carcinoma (HCC), and to analyze the role of Beclin-1Caspase-9 and p53 in the development of HCC and their correlation with the clinicopathological data. The prognosis of HCC was analyzed to provide a more effective basis for early detection, treatment and prognosis of HCC. Methods 108 cases of HBV virus-associated HCC, 30 cases of liver cirrhosis and 20 cases of normal liver tissue were collected. The expressions of Beclin-1 and Caspase-9 p53 were detected by immunohistochemical staining in three groups, and their relationship with clinicopathological parameters, 5-year survival time and tumor-free survival time of HCC were analyzed. Results the positive expression rate of Beclin-1 in HCC group was significantly lower than that in normal liver tissue group (蠂 ~ 2 / 5.575P ~ (0.016), liver cirrhosis group and normal liver tissue group. There was no significant difference in the positive expression of p53 between the liver cirrhosis group and the HCC group (蠂 ~ 2 / 3.704 / P ~ (0.054), 蠂 ~ (2 +) ~ (0.054) P ~ (0.815) p53 expression in the HCC group, which was higher than that in the normal liver tissue group and the liver cirrhosis group. The expression of Caspase-9 in HCC was significantly higher than that in normal liver tissue (蠂 ~ 2 ~ 2 ~ (4.349) P ~ (0.037), but between liver cirrhosis tissue and normal liver tissue and liver cirrhosis tissue and HCC tissue, the expression of Caspase-9 in HCC was significantly higher than that in normal liver tissue (蠂 ~ (2) (蠂 ~ (2) (蠂 ~ (2) 17.297 (P < 0.05), and the expression of Caspase-9 in HCC was higher than that in normal liver tissue (蠂 ~ (2). There was no significant difference in its expression (蠂 ~ 2 / 0.347P ~ (0.556); 蠂 ~ (2 +) 2.713P ~ (0.100). Beclin-1 expression in HCC was related to Edmondson's pathological grade (P ~ (0.010) and AFP (P ~ (0.047). It was associated with age, sex, tumor size, number and satellite foci, vascular tumor thrombus, cirrhosis, etc. The expression of p53 in HCC was not related to the pathological grade of Edmondson. It was associated with age, sex, tumor size, number of AFP and whether there were satellite foci, vascular thrombus, cirrhosis. The expression of Caspase-9 in HCC was not correlated with the pathological grade of Edmondson (P0. 001) and whether there was a satellite tumor (P0. 005). It was associated with age, sex of AFP, size and number of tumor, whether there were vascular thrombus and cirrhosis. There was no correlation between the expression of Beclin-1 and p53 in HCC. There was a positive correlation between the expression of Beclin-1 and Caspase-9 in HCC. The effect of Beclin-1 p53 and Caspase-9 on the prognosis was analyzed. It was found that the survival time and tumor-free survival time of the patients with high expression of .Beclin-1 related to the prognosis of patients were longer than those of the cases with low expression of P0. 001 and P0. 006. The survival time and tumor-free survival time of the cases with positive expression of Caspase-9 were longer than those with negative expression of P0. 025 and p53. The survival time was longer than that in the positive cases, but there was no significant difference in the survival time without tumor. Conclusion the low expression of Beclin-1 in hepatocellular carcinoma and the high expression of Caspase-9 and p53 are negatively correlated with the expression of p53. The expression of Caspase-9 was positively correlated with the expression of Caspase-9. Beclin-1 and p53 may be related to the occurrence and development of HCC. Beclin-1 p53 and Caspase-9 may be important indexes to judge the biological behavior and prognosis of HCC.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.7

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