Erbin在乳腺癌中的表达及其与HER2、p53等表达状态之间的关系探讨

发布时间：2018-05-11 10:15

本文选题：乳腺癌 + Erbin　；参考：《苏州大学》2016年硕士论文

【摘要】：研究背景:乳腺癌作为女性最常见恶性肿瘤之一,是女性恶性肿瘤中排名第二致死率的疾病。据统计,仅在全美,每年新发病例约23万余例,并且导致了超过4万妇女死于该疾病。作为对人类健康具有严重威胁的恶性肿瘤,乳腺癌始终是生物医学界研究的热点之一。近年来,通过先进的全数字钼靶X线检查、辅助疗法以及针对转移性患者的治疗进展,乳腺癌的早期发现率及治疗方式取得了很大的进步。然而,对于晚期诊断以及晚期发生转移的乳腺癌的患者,其总的治疗收益仍不能令人满意,这就需要科研工作者从不同的角度来研究和探讨这种疾病。作为LAP蛋白家族成员之一,Erbin由氨基端的16个LRR基序(23-391个残基)以及羧基端的一个PDZ结构域(1280-1368个残基)组成。除了能与HER2相互作用之外,近年来随着研究的深入,发现了许多的Erbin相互作用蛋白,充分体现出其生物学功能的多样性;因而Erbin在乳腺癌中的表达情况如何及其与乳腺癌中的重要肿瘤相关基因的关系值得深入研究。研究方法:我们首先采用免疫组织化学染色法(IHC)对来自临床的已经确诊为良性乳腺疾病及乳腺癌患者的标本进行Erbin表达的染色检测,以此来了解Erbin在这些组织中的表达情况。其次,通过IHC染色,获得了HER2、p53、Ki67这些与治疗及预后相关的指标在乳腺恶性肿瘤中的表达情况,同时收集了腋窝淋巴结转移和肿瘤直径在内的临床病理特征资料。将Erbin的表达与这些指标相比较,以不同的角度去探讨乳腺癌这种疾病。研究结果:1.在乳腺良性疾病中Erbin的表达要明显低于乳腺癌患者中的表达。2.乳腺浸润性导管癌中,Erbin的表达与HER2的扩增相关,HER2阴性的病例Erbin的表达明显低于表达HER2的病例。3.乳腺浸润性导管癌中,Erbin的表达与p53表达相关,Erbin在p53阳性的患者中表达高于p53阴性的病例。4.在乳腺浸润性导管癌中,Erbin的表达与Ki67、腋窝淋巴结转移与肿瘤直径在内的临床病理特征不相关。结论:乳腺癌中,Erbin的高表达与HER2依赖性乳腺肿瘤细胞的增生关系密切,Erbin能够稳定HER2并促进HER2的扩增;同时Erbin的表达可能有助于p53的稳定以利于其在肿瘤细胞内的积累而达到促进肿瘤的作用。
[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.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R737.9

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