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Rap1GAP在結(jié)腸癌中的表達(dá)及其甲基化水平

發(fā)布時(shí)間:2018-06-02 23:08

  本文選題:結(jié)腸癌 + Rap1GAP; 參考:《山西醫(yī)科大學(xué)》2015年碩士論文


【摘要】:目的:結(jié)腸癌是消化系統(tǒng)常見(jiàn)惡性腫瘤之一,目前,大多數(shù)研究均明確顯示,近年來(lái)全球結(jié)腸癌的發(fā)病率有明顯增高的趨勢(shì),且趨于年輕化。一般情況下結(jié)腸癌起病隱匿,早期多無(wú)癥狀或癥狀不典型,易被忽視,從而影響了早期診斷及治療,發(fā)現(xiàn)時(shí)已出現(xiàn)轉(zhuǎn)移,失去了根治機(jī)會(huì),嚴(yán)重影響預(yù)后。所以癌癥如何早期診斷、其發(fā)病機(jī)制如何是目前腫瘤研究的熱點(diǎn)。近年來(lái)分子生物學(xué)及表觀遺傳學(xué)的發(fā)展和應(yīng)用,發(fā)現(xiàn)了許多與腫瘤浸潤(rùn)轉(zhuǎn)移相關(guān)的基因及其可能的影響機(jī)制。作為抑癌基因,Rap1GAP在多數(shù)腫瘤中表達(dá)明顯下調(diào),隨著表觀遺傳學(xué)方面的研究逐步深入,Rap1GAP啟動(dòng)子甲基化與腫瘤的關(guān)系越來(lái)越受到科學(xué)家們的重視。本文擬通過(guò)應(yīng)用免疫組化法及定量甲基化PCR(quantitative methylation specific PCR,q-MSP)檢測(cè)Rap1GAP在結(jié)腸癌中的表達(dá)情況及其啟動(dòng)子甲基化情況,旨在為結(jié)腸癌的早期診斷、靶向治療、早期治療、改善預(yù)后等方面提供基礎(chǔ)理論依據(jù)及研究方向。方法:應(yīng)用免疫組化技術(shù)檢測(cè)Rap1GAP的表達(dá)情況;比較組間Rap1GAP表達(dá)的差異;使用定量甲基化PCR(quantitative methylation specific PCR,q-MSP)技術(shù)檢測(cè)Rap1GAP基因的啟動(dòng)子區(qū)甲基化水平差異。并比較組間Rap1GAP基因啟動(dòng)子區(qū)甲基化水平的差異。結(jié)果:在結(jié)腸癌組織中,Rap1GAP蛋白的表達(dá)較癌旁相對(duì)正常組織及結(jié)腸腺瘤均有所下降(P0.05),而結(jié)腸腺瘤組與癌旁相對(duì)正常組織組的表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)腸癌組甲基化率明顯高于結(jié)腸腺瘤組及癌旁正常組織組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:抑癌基因Rap1GAP與結(jié)腸癌的發(fā)生發(fā)展有關(guān)。Rapl GAP蛋白的低表達(dá)與Rap1GAP啟動(dòng)子高甲基化有關(guān)。Rap1GAP啟動(dòng)子高甲基化有可能作為結(jié)腸癌早期診斷的靶標(biāo)。
[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.
【學(xué)位授予單位】:山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2015
【分類(lèi)號(hào)】:R735.35

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