Rap1GAP在结肠癌中的表达及其甲基化水平

发布时间：2018-06-02 23:08

本文选题：结肠癌 + Rap1GAP　；参考：《山西医科大学》2015年硕士论文

【摘要】：目的:结肠癌是消化系统常见恶性肿瘤之一,目前,大多数研究均明确显示,近年来全球结肠癌的发病率有明显增高的趋势,且趋于年轻化。一般情况下结肠癌起病隐匿,早期多无症状或症状不典型,易被忽视,从而影响了早期诊断及治疗,发现时已出现转移,失去了根治机会,严重影响预后。所以癌症如何早期诊断、其发病机制如何是目前肿瘤研究的热点。近年来分子生物学及表观遗传学的发展和应用,发现了许多与肿瘤浸润转移相关的基因及其可能的影响机制。作为抑癌基因,Rap1GAP在多数肿瘤中表达明显下调,随着表观遗传学方面的研究逐步深入,Rap1GAP启动子甲基化与肿瘤的关系越来越受到科学家们的重视。本文拟通过应用免疫组化法及定量甲基化PCR(quantitative methylation specific PCR,q-MSP)检测Rap1GAP在结肠癌中的表达情况及其启动子甲基化情况,旨在为结肠癌的早期诊断、靶向治疗、早期治疗、改善预后等方面提供基础理论依据及研究方向。方法:应用免疫组化技术检测Rap1GAP的表达情况;比较组间Rap1GAP表达的差异;使用定量甲基化PCR(quantitative methylation specific PCR,q-MSP)技术检测Rap1GAP基因的启动子区甲基化水平差异。并比较组间Rap1GAP基因启动子区甲基化水平的差异。结果:在结肠癌组织中,Rap1GAP蛋白的表达较癌旁相对正常组织及结肠腺瘤均有所下降(P0.05),而结肠腺瘤组与癌旁相对正常组织组的表达差异无统计学意义。结肠癌组甲基化率明显高于结肠腺瘤组及癌旁正常组织组,差异有统计学意义(P0.05)。结论:抑癌基因Rap1GAP与结肠癌的发生发展有关。Rapl GAP蛋白的低表达与Rap1GAP启动子高甲基化有关。Rap1GAP启动子高甲基化有可能作为结肠癌早期诊断的靶标。
[Abstract]:Objective: colon cancer is one of the most common malignant tumors in digestive system. At present, most researches show that the incidence of colon cancer in the world is increasing obviously in recent years and tends to be younger. In general, colon cancer has hidden onset, asymptomatic or atypical symptoms in the early stage, which is easy to be ignored, thus affecting the early diagnosis and treatment, it has been found to have metastases, lost the opportunity of radical cure, and seriously affected the prognosis. Therefore, how to diagnose cancer early and how to pathogenesis is the focus of cancer research. In recent years, with the development and application of molecular biology and epigenetics, many genes related to tumor invasion and metastasis and their possible mechanism have been discovered. The expression of Rap1GAP as a tumor suppressor gene is down-regulated in most tumors. With the study of epigenetics, the relationship between methylation of Rap1GAP promoter and tumor has been paid more and more attention by scientists. The expression of Rap1GAP in colon cancer and its promoter methylation were detected by immunohistochemical method and quantitative methylation PCR(quantitative methylation specific PCRQ-MSPs. The aim of this study was to provide early diagnosis, targeted therapy and early treatment for colon cancer. To improve prognosis and provide basic theoretical basis and research direction. Methods: the expression of Rap1GAP was detected by immunohistochemical technique, the difference of Rap1GAP expression between groups was compared, and the methylation level of Rap1GAP gene promoter region was detected by quantitative methylation PCR(quantitative methylation specific PCRRnq-MSPI technique. The methylation level of promoter region of Rap1GAP gene was compared among different groups. Results: the expression of Rap1GAP protein in colon cancer tissue was lower than that in adjacent normal tissue and colon adenoma, but there was no significant difference between colon adenoma group and adjacent normal tissue group. The methylation rate in colon cancer group was significantly higher than that in colon adenoma group and adjacent normal tissue group (P 0.05). Conclusion: the low expression of Rapl GAP protein is related to the hypermethylation of Rap1GAP promoter. Rap1GAP promoter hypermethylation may be a target for early diagnosis of colon cancer.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.35

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