本文選題：ARHI + BECN1��； 參考：《大連醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:乳腺癌是一種臨床常見的惡性腫瘤,威脅世界女性健康,近年來其發(fā)病率持續(xù)升高,并且發(fā)病趨勢逐漸年輕化。癌基因和抑癌基因均存在于機(jī)體正常細(xì)胞內(nèi),正常情況下,它們以正負(fù)信號“平衡狀態(tài)”調(diào)節(jié)細(xì)胞的增殖分化,當(dāng)內(nèi)在、外界因素使得抑癌基因失活或癌基因激活后,這種“平衡狀態(tài)”被打破,從而導(dǎo)致正常細(xì)胞向癌細(xì)胞的轉(zhuǎn)化。乳腺癌的發(fā)生、發(fā)展是多種基因變異累積的病變過程,抑癌基因的失活在乳腺癌的演變過程中發(fā)揮重要作用。ARHI(Aplasia Ras homolog memberⅠ),又名NOEY2或DIRAS3,屬小G蛋白Ras超家族,是該家族第一個(gè)被報(bào)道的抑癌基因,在腫瘤的生長侵襲和自噬過程中起重要作用。BECN1是酵母中Atg6的同源物,可與Ⅲ型PI3K及Vps34相結(jié)合啟動自噬,和ARHI一樣,與腫瘤和自噬也有密不可分的聯(lián)系。既往研究表明,ARHI和BECN1在腫瘤中均表現(xiàn)為抑癌效應(yīng),在乳腺癌、卵巢癌、胰腺癌等多種惡性腫瘤中表達(dá)下調(diào)/缺失,但針對二者之間相關(guān)性的研究尚不多見。目的:通過檢測ARHI和BECN1在乳腺良性病變、乳腺癌及相應(yīng)癌旁組織中的表達(dá)水平,分析二者與乳腺癌臨床病理參數(shù)之間的關(guān)系,探討ARHI和BECN1在乳腺癌中的臨床意義;通過分析二者在乳腺癌各分子亞型間的表達(dá)差異,為臨床篩選高侵襲性乳腺癌提供理論依據(jù),從而指導(dǎo)臨床治療。方法:收集2015年01月~2016年12月于大連醫(yī)科大學(xué)第二臨床學(xué)院、大連市中心醫(yī)院接受手術(shù)治療的組織蠟塊標(biāo)本123例,其中乳腺良性病變24例、乳腺癌84例及相應(yīng)癌旁組織15例。應(yīng)用免疫組織化學(xué)方法(SP法)檢測乳腺良性病變、乳腺癌及相應(yīng)癌旁組織中ARHI、BECN1的表達(dá)情況;應(yīng)用統(tǒng)計(jì)學(xué)方法分析二者與乳腺癌臨床病理參數(shù)的關(guān)系及它們在乳腺癌中的表達(dá)相關(guān)性。結(jié)果:1、ARHI在乳腺良性病變、乳腺癌、癌旁組織中的陽性表達(dá)率分別為87.5%(21/24)、46.4%(39/84)和93.3%(14/15),在乳腺癌組織中的陽性表達(dá)率明顯低于另兩組,差異具有顯著統(tǒng)計(jì)學(xué)意義(P0.01)。ARHI在乳腺癌中的表達(dá)與癌組織的病理分化程度、淋巴結(jié)轉(zhuǎn)移情況以及PR(孕激素受體)表達(dá)情況相關(guān)(P0.05),而與患者的發(fā)病年齡、月經(jīng)狀態(tài)、是否有腫瘤家族史、臨床分期、腫瘤大小、是否存在脈管癌栓或神經(jīng)侵犯、ER、Her-2及CK5/6無明顯相關(guān)性(P0.05)。2、BECN1在乳腺良性病變、乳腺癌、癌旁組織中的陽性表達(dá)率分別為91.7%(22/24)、51.2%(43/84)和86.7%(13/15),在乳腺癌組織中的陽性表達(dá)率明顯低于另兩組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。BECN1在乳腺癌中的表達(dá)與臨床分期、病理分化程度、淋巴結(jié)轉(zhuǎn)移情況、是否有脈管癌栓及Her-2表達(dá)情況相關(guān)(P0.05),而與發(fā)病年齡、月經(jīng)狀態(tài)、是否有腫瘤家族史、腫瘤大小、是否存在神經(jīng)侵犯、ER、PR及CK5/6無相關(guān)性(P0.05)。3、在84例乳腺癌組織中,ARHI與BECN1的表達(dá)呈正相關(guān)(相關(guān)系數(shù)r=0.288,P=0.008)。4、ARHI和BECN1在Luminal A與Her-2擴(kuò)增型乳腺癌中的陽性表達(dá)率高且接近,其次為Luminal B型,在三陰性乳腺癌中的陽性表達(dá)率均最低。在乳腺癌各分子亞型中,ARHI的表達(dá)差異具有統(tǒng)計(jì)學(xué)意義(x2=22.040,P=0.000),而BECN1的表達(dá)差異無統(tǒng)計(jì)學(xué)意義(x2=6.330,P=0.097)。結(jié)論:1、ARHI和BECN1在乳腺癌中低表達(dá),陽性表達(dá)率明顯低于癌旁組織和乳腺良性病變。2、ARHI和BECN1在Luminal A與Her-2擴(kuò)增型乳腺癌中的陽性表達(dá)率高且接近,在三陰性乳腺癌中表達(dá)率均最低;ARHI在乳腺癌各分子亞型中的表達(dá)差異有統(tǒng)計(jì)學(xué)意義。3、ARHI和BECN1在乳腺癌中的表達(dá)呈正相關(guān)。4、在乳腺癌中,ARHI與BECN1的聯(lián)合檢測有助于評估腫瘤惡性程度、判斷預(yù)后、指導(dǎo)臨床治療等。
[Abstract]:Background: breast cancer is a common malignant tumor which threatens the health of women in the world. In recent years, the incidence of breast cancer has been increasing, and the incidence trend is gradually younger. The oncogene and tumor suppressor genes are all in the normal cells of the body. Under normal circumstances, they regulate cell proliferation and differentiation with positive and negative signals "balance", when inherent, After external factors make the tumor suppressor gene inactivation or oncogene activation, this "balance state" is broken, which leads to the transformation of normal cells to cancer cells. The development of breast cancer is the accumulation of various gene mutations, and the inactivation of the tumor suppressor gene plays an important role in the evolution process of breast cancer.ARHI (Aplasia Ras homolo). G member I), also known as NOEY2 or DIRAS3, is a small G protein Ras superfamily, and is the first reported tumor suppressor gene in the family. It plays an important role in the growth invasion and autophagy of the tumor..BECN1 is the homology of Atg6 in yeast. It can be combined with type III PI3K and Vps34 to start autophagy, like ARHI, and also inseparable from tumor and autophagy. Previous studies have shown that both ARHI and BECN1 are tumor suppressor effects in the tumor, and are down-regulated and deleted in many malignant tumors such as breast, ovarian and pancreatic cancer. However, there are few studies on the correlation between the two. Objective: to detect the expression of ARHI and BECN1 in breast benign lesions, breast cancer and corresponding para cancerous tissues To analyze the relationship between the two and the clinicopathological parameters of breast cancer, to explore the clinical significance of ARHI and BECN1 in breast cancer, and to provide a theoretical basis for the clinical screening of high invasive breast cancer by analyzing the differences in the expression of the two subtypes of the breast cancer molecules, and to guide the clinical treatment. Methods: to collect the December 2015 ~2016 year in 2015. The Second Clinical College of Dalian Medical University and Dalian central hospital received surgical treatment of 123 tissue paraffin specimens, including 24 benign breast lesions, 84 breast cancer and 15 corresponding para cancerous tissues. The expression of ARHI and BECN1 in breast benign lesions, breast cancer and corresponding para cancerous tissues was detected by SP method. The relationship between the two and the clinicopathological parameters of breast cancer and their correlation in breast cancer were statistically analyzed. Results: 1, the positive expression rate of ARHI in benign breast lesions, breast cancer and para cancerous tissues was 87.5% (21/24), 46.4% (39/84) and 93.3% (14 /15), and the positive expression rate in breast cancer tissues was significantly lower than that of the other two. The difference has significant statistical significance (P0.01) the expression of.ARHI in breast cancer is related to the degree of pathological differentiation, lymph node metastasis and the expression of PR (progestin receptor) (P0.05), and the age of the patients, the state of menstruation, the family history of the tumor, the clinical stage, the size of the tumor, and whether there is a vascular tumor thrombus or whether there is a vascular tumor thrombus or whether or not. There was no significant correlation between ER, Her-2 and CK5/6 (P0.05).2. The positive expression rate of BECN1 in benign breast lesions, breast cancer and adjacent tissues was 91.7% (22/24), 51.2% (43/84) and 86.7% (13/15), and the positive expression rate in breast cancer tissues was significantly lower than that in the other two groups, and the difference was statistically significant (P0.05).BECN1 in breast cancer The clinical stage, the degree of pathological differentiation, lymph node metastasis, the correlation of the vascular tumor thrombus and the expression of Her-2 (P0.05), and the age, menstruation, the family history of the tumor, the size of the tumor, the existence of nerve invasion, the ER, PR and CK5/6 non correlation (P0.05).3, and the expression of ARHI and BECN1 in 84 cases of breast cancer. The positive expression rate of correlation coefficient r=0.288, P=0.008).4, ARHI and BECN1 in Luminal A and Her-2 amplification breast cancer is high and close, followed by Luminal B type, and the positive expression rate in three negative breast cancers is the lowest. There was no statistical significance (x2=6.330, P=0.097). Conclusion: 1, ARHI and BECN1 were low expression in breast cancer, and the positive expression rate was significantly lower than that of para cancerous tissues and benign breast lesions. The positive expression rate of ARHI and BECN1 in Luminal A and Her-2 expanded breast cancer was high and close, and the expression rate in three negative breast cancers was the lowest; ARHI in breast cancer. The expression differences in the subtypes of each molecule are statistically significant.3, the expression of ARHI and BECN1 in breast cancer is positively correlated with.4. In breast cancer, the combined detection of ARHI and BECN1 can help to evaluate the malignancy of the tumor, judge the prognosis, and guide the clinical treatment.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9

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本文編號：2067227