雌激素受体和共调节因子在人结直肠癌组织中差异性表达

发布时间：2018-03-14 05:08

本文选题：雌激素受体beta　切入点：共调节因子包括叉头蛋白A1　出处：《广西医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的：近年来,越来越多的证据显示雌激素受体(ER)信号通路参与结直肠癌的发生发展过程。但是关于ER在此癌变过程中的具体作用却不是十分明确,ER在癌变过程参与的信号分子通路及其作用也不清楚,本实验的目的是在人结直肠组织中应用免疫组织化学法和荧光定量PCR两种方法检测雌激素受体beta (ERβ)以及共调节因子包括叉头蛋白A1(FOXA1)、核受体共激活因子3(NCOA3/AIB1)、核受体共激活因子2(NCOA2/TIF2)和脯氨酸-谷氨酸-亮氨酸富集蛋白1 (PELP1)在蛋白水平和转录水平上的表达情况,并结合相关临床病理资料共同分析这些因子在结直肠癌发生发展过程中可能的作用。方法：收集广西医科大学第一附属医院2014-03至2014-11行结直肠癌切除术的结直肠癌及其配对正常组织标本200例,其中80例用于荧光定量PCR来检测ERβ、FOXA1、AIB1、TIF2和PELP1在转录水平的表达,120例应用免疫组织化学法检测五种因子在蛋白水平上的表达。在癌组织和配对正常组织中比较是否存在差异性表达。分析五个指标在转录水平和蛋白水平分别于临床病理资料的相关性。应用ROC曲线来判断五种指标在结直肠癌中的预测价值。结果：与配对正常组织相比,ERβ在结直肠癌组织中均存在转录水平和蛋白水平的表达降低,且有统计学意义(P0.001,P0.001)。FOXA1在癌组织中也同时存在转录水平和蛋白水平的表达缺失(P=0.032,P0.001)。AIB1也发现相同现象(转录水平P0.001,蛋白水平P0.001)。TIF2在癌组织中转录水平表达下降(P0.001),但在蛋白水平上却无差异性表达(P=0.438)。PELP1在转录水平上表达升高但是在蛋白水平上表达降低且都有统计学意义(P=0.013,P0.001)。在相关性分析上发现ERβ和AIB1、ERp和PELP1、AIB1和PELP1三组在转录水平和蛋白水平同时存在正相关。同时应用ROC曲线来判断四种因子在结直肠癌中是否具有诊断价值,发现除FOXA1(P=0.266)外,ERβ、AIB1、TIF2和PELP1均有诊断预测价值(分别为P0.001.P0.001、P=0.011.P=0.009).表达量与临床病理资料分析中发现ERβ、AIB1、FOXA1、TIF2和PELP1的表达与一些有关诊断和预后的临床病理因素存在相关性,包括肿瘤大小、T分期(肿瘤浸润深度),和N分期(淋巴结转移范围),临床分期,神经侵犯,脉管侵犯。结论：ERβ、AIB1、FOXA1、TIF2和PELP1都可能参与结直肠癌发生发展过程。其中ERβ、AIB1、FOXA1和PELP1可能主要起抑制肿瘤化的保护性作用。TIF2的结论不一致,但根据差异性表达可能主要是促癌作用。ERp.AIB1和PELP1三者的关系更为密切,可能直接形成蛋白复合物参与调节下游通路。雌激素受体通路非常复杂,本实验仅能部分说明其中一些相关性,关于信号通路因子在结直肠癌中的具体作用仍需更多基础实验。
[Abstract]:Objective: in recent years, There is more and more evidence that estrogen receptor ER) signaling pathway is involved in the development of colorectal cancer. However, the specific role of ER in the carcinogenesis process is not very clear about the signal molecules involved in the carcinogenesis of colorectal cancer. The pathway and its effects are also unclear. The aim of this study was to detect estrogen receptor ER 尾 (ER 尾) by immunohistochemistry and fluorescence quantitative PCR in human colorectal tissues, and to detect coregulatory factors such as forkhead protein A1, nuclear receptor coactivator 3NCOA3 / AIB1, nuclear receptor coreceptor coreceptor coactivator 3NCOA3 / AIB1a, nuclear receptor coactivator 3nCOA3 / AIB1, nuclear receptor coactivator 3nCOA3 / AIB1a. The expression of activator 2NCOA2 / TIF2 and proline glutamic acid-leucine enriched protein 1 (PELP1) at the protein and transcription levels, The possible role of these factors in the occurrence and development of colorectal cancer was analyzed in conjunction with relevant clinicopathological data. Methods: the first affiliated Hospital of Guangxi Medical University from 2014-03 to 2014-11 was collected for colorectal cancer undergoing colorectal cancer resection. And its matched normal tissue specimens, 200 cases, Among them, 80 cases were used for fluorescent quantitative PCR to detect the expression of TIF2 and PELP1 at transcriptional level. 120 cases were examined for the expression of five factors at the protein level by immunohistochemical method. The presence of TIF2 and PELP1 at the protein level was compared between cancer tissues and matched normal tissues. Differential expression. Analysis of the correlation between transcription level and protein level of five markers in clinicopathological data. ROC curve was used to determine the predictive value of five indicators in colorectal cancer. Results: matched normal tissue. Compared with the expression of ER 尾 in colorectal cancer tissues, the expression of ER 尾 was decreased in both the transcriptional and protein levels. There was also a significant difference in the expression of both transcription level and protein level in cancer tissues. The same phenomenon was found in P0.001, P0.001, P0.001, TIF2, P0.001, P0.001, P0.001, P0.001 and P0.001, respectively, but the same phenomenon was also found in P0.032, P0.001, AIB1 (P0.001, P0.001, P0.001, TIF2, P0.001, P0.001, P0.001, P0.001, P0.001, P0.001, P0.001, P0.001 and P0.001, respectively. However, there was no difference in the expression of Pn0. 438. PELP1 at the transcriptional level, but decreased at the protein level. The results of correlation analysis showed that ER 尾 and AIB1 + AIB1 and PELP1, AIB1 and PELP1 had the same transcriptional and protein levels as those of ER 尾 and AIB1, P0. 013, P0. 001 and P0. 001. The results of correlation analysis showed that ER 尾, AIB1, AIB1, AIB1 and PELP1 had the same transcription and protein levels. At the same time, the ROC curve was used to determine the diagnostic value of the four factors in colorectal cancer. It was found that both ER 尾 AIB1TIF2 and PELP1 had diagnostic and predictive value (P0.001.P0.001, P0.011.P0. 009). The expression of ER 尾 AIB1FXA1TIF2 and PELP1 were correlated with some clinicopathological factors related to the diagnosis and prognosis, and the expression of ER 尾 AIB1 FXA1TIF2 and PELP1 were found to be correlated with the clinicopathological factors of diagnosis and prognosis. These include tumor size T stage (depth of tumor invasion), and N stage (lymph node metastasis range, clinical stage, nerve invasion, Conclusion both TIF2 and PELP1 may be involved in the development of colorectal cancer. The conclusions of ER 尾 AIB1 FOXA1 and PELP1 may mainly play a protective role in inhibiting tumorigenesis. TIF2 is not consistent. However, the differential expression may be mainly related to carcinogenesis. ERp.AIB1 and PELP1 are more closely related, and may be directly formed protein complex involved in regulation of downstream pathway. Estrogen receptor pathway is very complex. This experiment can only partially explain some of these correlations, and more basic experiments are needed on the role of signal pathway factors in colorectal cancer.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.34

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