本文選題：卵巢癌 + 漿液性��； 參考：《承德醫(yī)學(xué)院》2017年碩士論文

【摘要】：卵巢癌是女性生殖系統(tǒng)最為常見的惡性腫瘤之一,在女性生殖系統(tǒng)惡性腫瘤中發(fā)病率居第二位,死亡率居第一位。卵巢漿液性癌(ovarian serous carcinoma,OSC)是卵巢惡性腫瘤中最常見的組織學(xué)類型,約占所有卵巢惡性腫瘤的40%。復(fù)發(fā)率和死亡率高、預(yù)后差是其主要特點(diǎn),因其早期癥狀不典型,多數(shù)患者確診時(shí)病情已進(jìn)展至晚期。目前國際上對卵巢癌的治療是以手術(shù)為主,結(jié)合化療的綜合療法。盡管多手段的治療在某種程度上延緩了患者的生存期,但是效果并不明顯。而患者對化療的耐藥性,又成為臨床治療的阻礙。所以尋找有效的早期診斷技術(shù)及治療方案對于臨床治療十分關(guān)鍵。研究顯示卵巢漿液性癌的發(fā)生、發(fā)展是一個(gè)多基因參與、多階段發(fā)展的復(fù)雜過程,包括細(xì)胞凋亡的異常,生長因子和其受體相互作用等等。而細(xì)胞凋亡又是近期的研究熱點(diǎn)。Apaf-1(凋亡蛋白酶活化因子-1)是一個(gè)多功能結(jié)構(gòu)域的銜接蛋白。其功能涉及細(xì)胞凋亡,增殖和分化等多個(gè)方面。人體內(nèi)一系列信號的轉(zhuǎn)導(dǎo)級聯(lián)反應(yīng),都是通過Apaf-1為靶向而進(jìn)行凋亡體的調(diào)節(jié)。Apaf-1通過線粒體通路誘導(dǎo)細(xì)胞凋亡,是線粒體介導(dǎo)通路中一個(gè)關(guān)鍵的促凋亡因子。Apaf-1表達(dá)異常與多種惡性腫瘤發(fā)生發(fā)展密切相關(guān)。Caspase是一組半胱氨酸天冬氨酸特異性蛋白酶家族,該家族為近年來研究發(fā)現(xiàn)的執(zhí)行細(xì)胞凋亡的重要蛋白,是細(xì)胞凋亡的核心機(jī)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級聯(lián)反應(yīng)上游,是Caspase家族引起細(xì)胞凋亡的最主要的成分之一,其在組織中的低表達(dá)與多種腫瘤的發(fā)生發(fā)展相關(guān)。p53是研究最廣泛的腫瘤抑制基因,超過50%的惡性腫瘤中,可以檢測到該基因的突變。其核蛋白產(chǎn)物在阻滯細(xì)胞增長分化、促進(jìn)細(xì)胞凋亡等方面有著極其重要作用。突變型p53阻滯細(xì)胞異常增長的作用消失,促進(jìn)細(xì)胞的惡性轉(zhuǎn)化,致使腫瘤發(fā)生。目的:檢測apaf-1、caspase-9和p53在osc的表達(dá)情況,分析三者與osc臨床病理因素間的關(guān)系以及apaf-1、caspase-9和p53在osc中表達(dá)的相關(guān)性。探討apaf-1、caspase-9和p53在osc發(fā)生、發(fā)展中的作用,為osc的發(fā)生、發(fā)展及臨床特異性靶向治療提供更多理論依據(jù)。方法:采用免疫組化envision法檢測apaf-1、caspase-9和p53蛋白在45例osc,60例卵巢漿液性囊腺瘤和32例卵巢交界性漿液性囊腺瘤中的表達(dá)情況。分析apaf-1、caspase-9和p53的表達(dá)與osc的年齡、病理分級、臨床分期和淋巴結(jié)轉(zhuǎn)移之間的相關(guān)性。采用spss19.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,apaf-1、caspase-9和p53在osc的表達(dá)及其與osc臨床病理因素間的相關(guān)性采用χ2檢驗(yàn),apaf-1、caspase-9和p53在osc中表達(dá)的相關(guān)關(guān)系采用spearman一致性檢驗(yàn),以p0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1、apaf-1在卵巢漿液性囊腺瘤、交界性漿液性囊腺瘤和osc中的表達(dá)率為75%(45/60)、46.9%(15/32)和24.4%(11/45)。osc中apaf-1的陽性率低于漿液性囊腺瘤和交界性漿液性囊腺瘤,差異明顯(p0.05)。caspase-9在卵巢漿液性囊腺瘤、交界性漿液性囊腺瘤和osc中的陽性表達(dá)分別為83.3%(50/60)、56.3%(18/32)和28.9%(13/45),caspase-9在osc中的陽性率低于漿液性囊腺瘤和交界性漿液性囊腺瘤,差異顯著(p0.05)。p53在osc中的陽性表達(dá)率為46.7%(21/45),高于漿液性囊腺瘤的5%(3/60)和交界性漿液性囊腺瘤的9.4%(3/32),差異有統(tǒng)計(jì)學(xué)意義(p0.05)。2、apaf-1與osc的病理分級、臨床分期及淋巴結(jié)轉(zhuǎn)移有關(guān)(p0.05),和患者年齡無明顯相關(guān)性。caspase-9與osc的病理分級、臨床分期及淋巴結(jié)轉(zhuǎn)移有關(guān)(p0.05),與患者的年齡無關(guān)。p53與osc患者的年齡,病理分級,臨床分期和淋巴結(jié)轉(zhuǎn)移有關(guān)(p0.05)。3、在osc中,apaf-1和caspase-9表現(xiàn)為低表達(dá)并呈正相關(guān)(p0.05),apaf-1和p53的表達(dá)呈正相關(guān)(p0.05),caspase-9與p53的表達(dá)無明顯相關(guān)性。結(jié)論:Apaf-1和Caspase-9在OSC中表現(xiàn)為低表達(dá),其陽性表達(dá)率均明顯低于卵巢漿液性囊腺瘤和交界性漿液性囊腺瘤,p53在OSC中的陽性率高于卵巢漿液性囊腺瘤和交界性漿液性囊腺瘤。提示三者均參與了OSC的發(fā)生發(fā)展。Apaf-1和Caspase-9的表達(dá)與患者的年齡無相關(guān)性,與OSC的病理分級、臨床分期及淋巴結(jié)轉(zhuǎn)移關(guān)系密切,p53的表達(dá)與OSC患者的年齡、病理分級、臨床分期和淋巴結(jié)轉(zhuǎn)移有關(guān)。提示三者均參與了OSC的浸潤與轉(zhuǎn)移。在OSC中Apaf-1和Caspase-9呈正相關(guān)關(guān)系,說明在抑制OSC的發(fā)生發(fā)展過程中Apaf-1和Caspase-9可能起到了協(xié)同作用,聯(lián)合檢測Apaf-1和Caspase-9對判斷OSC的發(fā)生發(fā)展和預(yù)后可能有指導(dǎo)意義。Apaf-1和p53在OSC中的表達(dá)呈正相關(guān),提示二者可能在作用過程中具有一定的關(guān)聯(lián)性,可能共同參與了OSC的發(fā)生。但Caspase-9和p53在OSC中的表達(dá)無相關(guān)關(guān)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.
【學(xué)位授予單位】：承德醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.31

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