Erbin在乳腺癌中的表達(dá)及其與HER2、p53等表達(dá)狀態(tài)之間的關(guān)系探討
本文選題:乳腺癌 + Erbin; 參考:《蘇州大學(xué)》2016年碩士論文
【摘要】:研究背景:乳腺癌作為女性最常見惡性腫瘤之一,是女性惡性腫瘤中排名第二致死率的疾病。據(jù)統(tǒng)計(jì),僅在全美,每年新發(fā)病例約23萬余例,并且導(dǎo)致了超過4萬婦女死于該疾病。作為對(duì)人類健康具有嚴(yán)重威脅的惡性腫瘤,乳腺癌始終是生物醫(yī)學(xué)界研究的熱點(diǎn)之一。近年來,通過先進(jìn)的全數(shù)字鉬靶X線檢查、輔助療法以及針對(duì)轉(zhuǎn)移性患者的治療進(jìn)展,乳腺癌的早期發(fā)現(xiàn)率及治療方式取得了很大的進(jìn)步。然而,對(duì)于晚期診斷以及晚期發(fā)生轉(zhuǎn)移的乳腺癌的患者,其總的治療收益仍不能令人滿意,這就需要科研工作者從不同的角度來研究和探討這種疾病。作為L(zhǎng)AP蛋白家族成員之一,Erbin由氨基端的16個(gè)LRR基序(23-391個(gè)殘基)以及羧基端的一個(gè)PDZ結(jié)構(gòu)域(1280-1368個(gè)殘基)組成。除了能與HER2相互作用之外,近年來隨著研究的深入,發(fā)現(xiàn)了許多的Erbin相互作用蛋白,充分體現(xiàn)出其生物學(xué)功能的多樣性;因而Erbin在乳腺癌中的表達(dá)情況如何及其與乳腺癌中的重要腫瘤相關(guān)基因的關(guān)系值得深入研究。研究方法:我們首先采用免疫組織化學(xué)染色法(IHC)對(duì)來自臨床的已經(jīng)確診為良性乳腺疾病及乳腺癌患者的標(biāo)本進(jìn)行Erbin表達(dá)的染色檢測(cè),以此來了解Erbin在這些組織中的表達(dá)情況。其次,通過IHC染色,獲得了HER2、p53、Ki67這些與治療及預(yù)后相關(guān)的指標(biāo)在乳腺惡性腫瘤中的表達(dá)情況,同時(shí)收集了腋窩淋巴結(jié)轉(zhuǎn)移和腫瘤直徑在內(nèi)的臨床病理特征資料。將Erbin的表達(dá)與這些指標(biāo)相比較,以不同的角度去探討乳腺癌這種疾病。研究結(jié)果:1.在乳腺良性疾病中Erbin的表達(dá)要明顯低于乳腺癌患者中的表達(dá)。2.乳腺浸潤(rùn)性導(dǎo)管癌中,Erbin的表達(dá)與HER2的擴(kuò)增相關(guān),HER2陰性的病例Erbin的表達(dá)明顯低于表達(dá)HER2的病例。3.乳腺浸潤(rùn)性導(dǎo)管癌中,Erbin的表達(dá)與p53表達(dá)相關(guān),Erbin在p53陽性的患者中表達(dá)高于p53陰性的病例。4.在乳腺浸潤(rùn)性導(dǎo)管癌中,Erbin的表達(dá)與Ki67、腋窩淋巴結(jié)轉(zhuǎn)移與腫瘤直徑在內(nèi)的臨床病理特征不相關(guān)。結(jié)論:乳腺癌中,Erbin的高表達(dá)與HER2依賴性乳腺腫瘤細(xì)胞的增生關(guān)系密切,Erbin能夠穩(wěn)定HER2并促進(jìn)HER2的擴(kuò)增;同時(shí)Erbin的表達(dá)可能有助于p53的穩(wěn)定以利于其在腫瘤細(xì)胞內(nèi)的積累而達(dá)到促進(jìn)腫瘤的作用。
[Abstract]:Background: breast cancer, as one of the most common malignant tumors in women, is the second leading cause of mortality in women. According to statistics, in the United States alone, about 230000 new cases each year, and caused more than 40, 000 women died of the disease. As a malignant tumor that poses a serious threat to human health, breast cancer has always been one of the hotspots in biomedical research. In recent years, through advanced digital mammography examination, adjuvant therapy and treatment progress for metastatic patients, the early detection rate and treatment methods of breast cancer have made great progress. However, for patients with advanced diagnosis and advanced metastatic breast cancer, the overall therapeutic benefits are still unsatisfactory, which requires researchers to study and discuss the disease from different angles. Erbin, a member of the LAP family, consists of 16 amino terminal LRR motifs (23-391 residues) and a carboxyl terminal PDZ domain (1280-1368 residues). In addition to the ability to interact with HER2, many Erbin interacting proteins have been found in recent years, which fully reflect the diversity of their biological functions. Therefore, the expression of Erbin in breast cancer and its relationship with important tumor-associated genes in breast cancer are worthy of further study. Methods: immunohistochemical staining was used to detect the expression of Erbin in patients with benign breast disease and breast cancer in order to understand the expression of Erbin in these tissues. Secondly, by IHC staining, the expression of HER2 + p53 / Ki67, which is related to the treatment and prognosis, was obtained, and the clinicopathological data including axillary lymph node metastasis and tumor diameter were collected. Compare the expression of Erbin with these markers and explore breast cancer from different angles. The result of the study was: 1. The expression of Erbin in benign breast diseases was significantly lower than that in breast cancer patients. 2. 2. The expression of Erbin in breast invasive ductal carcinoma was significantly lower than that in the case of HER2. The expression of Erbin in invasive ductal carcinoma of breast is related to the expression of p53. The expression of Erbin in p53 positive patients is higher than that in p53 negative cases. The expression of Erbin in invasive ductal carcinoma of breast was not correlated with the clinicopathological features of Ki67, axillary lymph node metastasis and tumor diameter. Conclusion: the high expression of Erbin in breast cancer is closely related to the proliferation of HER2 dependent breast tumor cells. Erbin can stabilize HER2 and promote the expansion of HER2. At the same time, the expression of Erbin may contribute to the stability of p53 and the accumulation of p53 in tumor cells.
【學(xué)位授予單位】:蘇州大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2016
【分類號(hào)】:R737.9
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