Apaf-1、Caspase-9和p53在卵巢浆液性癌中的表达及临床意义

发布时间：2018-06-11 18:59

本文选题：卵巢癌 + 浆液性　；参考：《承德医学院》2017年硕士论文

【摘要】：卵巢癌是女性生殖系统最为常见的恶性肿瘤之一,在女性生殖系统恶性肿瘤中发病率居第二位,死亡率居第一位。卵巢浆液性癌(ovarian serous carcinoma,OSC)是卵巢恶性肿瘤中最常见的组织学类型,约占所有卵巢恶性肿瘤的40%。复发率和死亡率高、预后差是其主要特点,因其早期症状不典型,多数患者确诊时病情已进展至晚期。目前国际上对卵巢癌的治疗是以手术为主,结合化疗的综合疗法。尽管多手段的治疗在某种程度上延缓了患者的生存期,但是效果并不明显。而患者对化疗的耐药性,又成为临床治疗的阻碍。所以寻找有效的早期诊断技术及治疗方案对于临床治疗十分关键。研究显示卵巢浆液性癌的发生、发展是一个多基因参与、多阶段发展的复杂过程,包括细胞凋亡的异常,生长因子和其受体相互作用等等。而细胞凋亡又是近期的研究热点。Apaf-1(凋亡蛋白酶活化因子-1)是一个多功能结构域的衔接蛋白。其功能涉及细胞凋亡,增殖和分化等多个方面。人体内一系列信号的转导级联反应,都是通过Apaf-1为靶向而进行凋亡体的调节。Apaf-1通过线粒体通路诱导细胞凋亡,是线粒体介导通路中一个关键的促凋亡因子。Apaf-1表达异常与多种恶性肿瘤发生发展密切相关。Caspase是一组半胱氨酸天冬氨酸特异性蛋白酶家族,该家族为近年来研究发现的执行细胞凋亡的重要蛋白,是细胞凋亡的核心机制。其中Caspase-9(半胱氨酸天冬氨酸蛋白酶-9)是促凋亡因子之一,位于Caspase级联反应上游,是Caspase家族引起细胞凋亡的最主要的成分之一,其在组织中的低表达与多种肿瘤的发生发展相关。p53是研究最广泛的肿瘤抑制基因,超过50%的恶性肿瘤中,可以检测到该基因的突变。其核蛋白产物在阻滞细胞增长分化、促进细胞凋亡等方面有着极其重要作用。突变型p53阻滞细胞异常增长的作用消失,促进细胞的恶性转化,致使肿瘤发生。目的:检测apaf-1、caspase-9和p53在osc的表达情况,分析三者与osc临床病理因素间的关系以及apaf-1、caspase-9和p53在osc中表达的相关性。探讨apaf-1、caspase-9和p53在osc发生、发展中的作用,为osc的发生、发展及临床特异性靶向治疗提供更多理论依据。方法:采用免疫组化envision法检测apaf-1、caspase-9和p53蛋白在45例osc,60例卵巢浆液性囊腺瘤和32例卵巢交界性浆液性囊腺瘤中的表达情况。分析apaf-1、caspase-9和p53的表达与osc的年龄、病理分级、临床分期和淋巴结转移之间的相关性。采用spss19.0软件进行统计学分析,apaf-1、caspase-9和p53在osc的表达及其与osc临床病理因素间的相关性采用χ2检验,apaf-1、caspase-9和p53在osc中表达的相关关系采用spearman一致性检验,以p0.05为差异有统计学意义。结果:1、apaf-1在卵巢浆液性囊腺瘤、交界性浆液性囊腺瘤和osc中的表达率为75%(45/60)、46.9%(15/32)和24.4%(11/45)。osc中apaf-1的阳性率低于浆液性囊腺瘤和交界性浆液性囊腺瘤,差异明显(p0.05)。caspase-9在卵巢浆液性囊腺瘤、交界性浆液性囊腺瘤和osc中的阳性表达分别为83.3%(50/60)、56.3%(18/32)和28.9%(13/45),caspase-9在osc中的阳性率低于浆液性囊腺瘤和交界性浆液性囊腺瘤,差异显著(p0.05)。p53在osc中的阳性表达率为46.7%(21/45),高于浆液性囊腺瘤的5%(3/60)和交界性浆液性囊腺瘤的9.4%(3/32),差异有统计学意义(p0.05)。2、apaf-1与osc的病理分级、临床分期及淋巴结转移有关(p0.05),和患者年龄无明显相关性。caspase-9与osc的病理分级、临床分期及淋巴结转移有关(p0.05),与患者的年龄无关。p53与osc患者的年龄,病理分级,临床分期和淋巴结转移有关(p0.05)。3、在osc中,apaf-1和caspase-9表现为低表达并呈正相关(p0.05),apaf-1和p53的表达呈正相关(p0.05),caspase-9与p53的表达无明显相关性。结论:Apaf-1和Caspase-9在OSC中表现为低表达,其阳性表达率均明显低于卵巢浆液性囊腺瘤和交界性浆液性囊腺瘤,p53在OSC中的阳性率高于卵巢浆液性囊腺瘤和交界性浆液性囊腺瘤。提示三者均参与了OSC的发生发展。Apaf-1和Caspase-9的表达与患者的年龄无相关性,与OSC的病理分级、临床分期及淋巴结转移关系密切,p53的表达与OSC患者的年龄、病理分级、临床分期和淋巴结转移有关。提示三者均参与了OSC的浸润与转移。在OSC中Apaf-1和Caspase-9呈正相关关系,说明在抑制OSC的发生发展过程中Apaf-1和Caspase-9可能起到了协同作用,联合检测Apaf-1和Caspase-9对判断OSC的发生发展和预后可能有指导意义。Apaf-1和p53在OSC中的表达呈正相关,提示二者可能在作用过程中具有一定的关联性,可能共同参与了OSC的发生。但Caspase-9和p53在OSC中的表达无相关关系。
[Abstract]:Ovarian cancer is one of the most common malignant tumors in the female reproductive system. The incidence of ovarian serous carcinoma (OSC) is the most common type of malignant tumor in female reproductive system. Ovarian serous carcinoma (ovarian) is the most common histological type of ovarian malignant tumor, which accounts for the recurrence rate and death of all ovarian malignant tumors. High rate, poor prognosis is its main feature, because the early symptoms are not typical, most patients have progressed to late stage. At present, the international treatment of ovarian cancer is based on surgery, combined with chemotherapy combined therapy. Although the treatment of multiple means has delayed the survival of the patients to some extent, but the effect is not obvious. The drug resistance of chemotherapy is also a hindrance to clinical treatment. Therefore, it is crucial to find effective early diagnostic techniques and treatments for clinical treatment. The study shows that the development of ovarian serous carcinoma is a multi gene participation, complex process of multistage development, including abnormal apoptosis, growth factors and their receptors. .Apaf-1 (apoptotic protease activating factor -1) is a cohesive protein in a multi-functional domain. Its function involves many aspects, such as cell apoptosis, proliferation and differentiation. The cascade reaction of a series of signals in the human body is the regulation of.Apaf-1 by targeting the apoptotic body through Apaf-1. Induction of apoptosis through mitochondrial pathway, a key apoptosis stimulating factor.Apaf-1 expression in mitochondrial pathway, is closely related to the development of a variety of malignant tumors..Caspase is a group of cysteine aspartate specific protease family. This family is an important protein for the execution of apoptosis in recent years. The core mechanism of apoptosis, Caspase-9 (cysteine aspartic proteinase -9) is one of the apoptosis promoting factors, located upstream of the Caspase cascade reaction, which is one of the most important components of apoptosis in the Caspase family. Its low expression in the tissue and the development of various tumors related.P53 are the most widely studied tumor suppressor. The gene mutation can be detected in more than 50% of the malignant tumor. Its nucleoprotein product plays an important role in blocking cell growth and differentiation, promoting cell apoptosis and so on. The abnormal growth of mutant p53 block cells disappears, promotes the malignant transformation of cells and causes the tumor to occur. Objective: to detect Apaf-1, caspase-9 And the expression of p53 in OSC, analysis of the relationship between three and OSC and the correlation between Apaf-1, caspase-9 and p53 in OSC, and explore the role of Apaf-1, caspase-9 and p53 in OSC occurrence and development, and provide more theoretical basis for the occurrence, development and clinical specific target treatment of OSC. The expression of Apaf-1, caspase-9 and p53 protein in 45 cases of OSC, 60 cases of serous cystadenoma and 32 cases of borderline serous cystadenoma of the ovary. The correlation between the expression of Apaf-1, caspase-9 and p53 and the age of OSC, the pathological grade, the clinical stage and lymph node metastasis were analyzed. The spss19.0 software was used for statistical analysis and a. The expression of paf-1, caspase-9 and p53 in OSC and its correlation with OSC clinicopathological factors were examined by x 2 test. The correlation between Apaf-1, caspase-9 and p53 in OSC was detected by Spearman consistency, with P0.05 difference statistically significant. Results: 1, Apaf-1 was in the ovarian cystadenoma, borderline serous cystadenoma and The rate of expression was 75% (45/60), and the positive rate of Apaf-1 in 46.9% (15/32) and 24.4% (11/45).Osc was lower than that of serous cystadenoma and borderline serous cystadenoma. The difference was significant (P0.05).Caspase-9 in serous cystadenoma, borderline serous cystadenoma and OSC, respectively, 83.3% (50/60), 56.3% (18/32) and 28.9% (13/45), caspase-9. The positive rate in OSC was lower than that of serous cystadenoma and borderline serous cystadenoma (P0.05), the positive rate of.P53 in OSC was 46.7% (21/45), higher than that of serous cystadenoma, 5% (3/60) and borderline serous cystadenoma (9.4% (3/32)), and the difference was statistically significant (P0.05).2, Apaf-1 and OSC, and clinical staging. Lymph node metastasis related (P0.05), and the age of the patients had no significant correlation with the pathological grades of.Caspase-9 and OSC, clinical staging and lymph node metastasis (P0.05). The age of the patients was not related to the age of the patients with.P53 and OSC, the pathological grade, the clinical staging and lymph node metastasis (P0.05).3, and in OSC, Apaf-1 and caspase-9 showed low expression and presented Positive correlation (P0.05), the expression of Apaf-1 and p53 was positively correlated (P0.05), and there was no significant correlation between the expression of caspase-9 and p53. Conclusion: the expression of Apaf-1 and Caspase-9 in OSC is low, and the positive rate is significantly lower than that of serous cystadenoma and borderline serous cystic adenoma, and the positive rate of p53 in OSC is higher than that in ovarian serous cystadenoma. Borderline serous cystadenoma. It is suggested that both of the three groups are involved in the occurrence and development of OSC, the expression of.Apaf-1 and Caspase-9 is not related to the age of the patients. It is closely related to the pathological classification of OSC, the clinical stage and lymph node metastasis. The expression of p53 is related to the age of the OSC patients, the pathological classification, the bed stage and lymph node metastasis. There is a positive correlation between Apaf-1 and Caspase-9 in OSC, which indicates that Apaf-1 and Caspase-9 may play a synergistic role in the process of inhibiting the occurrence and development of OSC. The joint detection of Apaf-1 and Caspase-9 may have a guiding significance in determining the occurrence and development and prognosis of OSC, which is positively correlated with the expression of p53 in the OSC, suggesting two They may have some relevance in the course of action and may participate in the occurrence of OSC. However, there is no correlation between Caspase-9 and p53 expression in OSC.
【学位授予单位】：承德医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.31

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