本文選題：MAL基因 + 食管鱗狀細(xì)胞癌　； 參考：《鄭州大學(xué)》2017年碩士論文

【摘要】：研究背景食管癌是常見的一種惡性腫瘤,我國是食管癌高發(fā)區(qū),并且發(fā)病率和病死率居世界首位。常見的病理類型有食管鱗狀細(xì)胞癌(esophageal squamous cell carcinoma,ESCC)和食管腺癌(esophageal adenocarcinoma,EAC),在我國以前者多見,約占90%以上,后者較少見,占10%左右。食管鱗狀細(xì)胞上皮重度不典型增生作為食管鱗癌癌前病變,是食管正常組織到惡變的一個(gè)重要過渡階段。食管癌的發(fā)生是多種因素參與、多階段、多步驟發(fā)展的復(fù)雜過程,其發(fā)生及發(fā)展主要與癌基因過度表達(dá)及抑癌基因失活有關(guān)�，F(xiàn)代腫瘤學(xué)認(rèn)為基因的改變主要涉及兩方面:遺傳學(xué)的改變和表觀遺傳學(xué)的異常;近年多種研究發(fā)現(xiàn)表觀遺傳學(xué)的異常改變?cè)谀[瘤的發(fā)生發(fā)展中起到非常重要的作用。表觀遺傳學(xué)是研究基因表達(dá)的學(xué)科,它是指基因表達(dá)的改變不依賴DNA序列的變化,其異�？蓪�(dǎo)致基因的表達(dá)沉默和缺失,而其中以DNA甲基化為研究最多的表觀遺傳調(diào)控形式之一[1];MAL基因位于人染色體2q13,它最早由Alonso等[2]于1987發(fā)現(xiàn)的一個(gè)在T細(xì)胞分化中晚期時(shí)表達(dá)的基因,該基因編碼一種高度疏水蛋白,最初推斷它與T淋巴細(xì)胞分化成熟有關(guān),后續(xù)研究證實(shí)MAL基因是遠(yuǎn)端質(zhì)膜和高爾基體之間囊泡轉(zhuǎn)運(yùn)和蛋白質(zhì)分選的作用成分之一。MAL在機(jī)體不同種類的細(xì)胞中均有表達(dá),對(duì)于細(xì)胞的正常結(jié)構(gòu)和功能有不可或缺的作用。多項(xiàng)試驗(yàn)研究證實(shí)MAL基因是一種候選的抑癌基因,并在很多腫瘤細(xì)胞中的表達(dá)減少或缺失,其啟動(dòng)子高度甲基化可能是基因失活和表達(dá)缺失的主要機(jī)制之一。不同的研究證實(shí)MAL基因甲基化存在于多種腫瘤中,但在食管黏膜上皮不典型增生中的研究少見,因此本文研究食管不典型增生過程中的MAL甲基化狀態(tài),及探討MAL甲基化在食管癌變發(fā)生發(fā)展中是否為一連續(xù)事件或有某種關(guān)聯(lián)性趨勢,以期對(duì)食管癌的早期診斷和篩查會(huì)提供一定的參考價(jià)值。目的1.研究MAL基因在食管鱗狀上皮細(xì)胞不典型增生、食管鱗狀細(xì)胞癌的甲基化狀態(tài)及臨床意義。2.MAL基因甲基化程度與食管癌變是否有關(guān)聯(lián)。方法隨機(jī)收集鄭州大學(xué)第一附屬醫(yī)院2014.10-2015.10年間食管鱗癌患者術(shù)后組織病理標(biāo)本共36例,其中包括癌組織及癌旁正常組織,其術(shù)前均未接受化療和放療等治療;另隨機(jī)收集鄭州大學(xué)第一附屬醫(yī)院病理科食管粘膜上皮不典型增生組織標(biāo)本共47例,其中輕度不典型增生13例,中度不典型增生21例,重度不典型增生13例;試驗(yàn)方法主要使用甲基化特異性PCR(MSP)技術(shù)檢測食管鱗癌、不典型增生及其對(duì)應(yīng)旁正常組織中MAL甲基化水平。統(tǒng)計(jì)學(xué)方法采用χ2檢驗(yàn)和Fisher確切概率法,以p0.05為有統(tǒng)計(jì)學(xué)意義,由SPSS 20.0軟件完成。結(jié)果1.食管鱗癌組織中MAL甲基化發(fā)生率為22例(61.1%),癌旁正常組織中MAL基因甲基化率為11.1%,兩組之間的甲基化發(fā)生率比較有統(tǒng)計(jì)學(xué)意義(p0.05)。2.食管上皮不典型增生共47例,MAL基因甲基化19例,(39.5%);其中輕度不典型增生13例,發(fā)生甲基化2例(15.4%),病變旁正常組織0例(0%)(p0.05),輕度不典型增生與對(duì)應(yīng)病變旁組織比較無差異;中度不典型增生21例,其中發(fā)生甲基化10例(47.6%),病變旁組織2例發(fā)生甲基化(9.5%),(p0.05),兩組比較有統(tǒng)計(jì)學(xué)意義;重度不典型增生共13例,其中發(fā)生甲基化7例(53.0%),病變旁正常組織1例發(fā)生甲基化(7.6%),(p0.05),兩組相比較有統(tǒng)計(jì)學(xué)意義。3.ESCC組織中MAL的甲基化水平與年齡、性別、侵襲深度、腫瘤大小、淋巴結(jié)轉(zhuǎn)移、腫瘤分期等食管癌相關(guān)臨床病理因素?zé)o顯著相關(guān)性(p0.05)。結(jié)論1.MAL基因甲基化改變發(fā)生于食管的輕、中和重度不典型增生組織,隨病變程度的增加,基因的甲基化頻率呈逐漸升高趨勢。2.食管鱗癌中DNA甲基化可能為MAL基因失活的機(jī)制之一,MAL甲基化檢測可能為今后食管癌早期輔助診斷提供一種新的篩查檢測方法。3.食管鱗癌中MAL基因甲基化頻率與相關(guān)病理因素,如年齡、性別、侵潤深度、腫瘤大小、淋巴結(jié)有無轉(zhuǎn)移、腫瘤分期無相關(guān)性。
[Abstract]:Background esophageal cancer is a common malignant tumor. Our country is a high incidence area of esophageal cancer, and the incidence and mortality rate are the first in the world. The common pathological types are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (esophageal adenocarcinoma, EAC), which are more common in our country, accounting for about 90%, The latter is relatively rare, accounting for about 10%. Severe atypical hyperplasia of the esophageal squamous cells is a precancerous lesion of esophageal squamous cell carcinoma. It is an important transitional stage of esophageal normal tissue to malignant transformation. The occurrence and development of esophageal cancer is a complex process of multiple factors participation, multistage and multi step development. The occurrence and development of esophageal squamous cell carcinoma are mainly associated with overexpression and inhibition of oncogenes. Oncology is related to inactivation of the oncogene. Modern oncology suggests that genetic changes are mainly involved in two aspects: genetic changes and epigenetic abnormalities; in recent years, a variety of studies have found that abnormal changes in epigenetics play a very important role in the development of tumors. Epigenetics is the subject of gene expression research, which refers to the gene table. The change does not depend on the changes in the DNA sequence, and its abnormality leads to the silence and deletion of gene expression, in which DNA methylation is one of the most important epigenetic regulation forms [1]; the MAL gene is located in the human chromosome 2q13, which is the first gene expressed in the late stage of differentiation of T cells by Alonso and other [2] in 1987. A highly hydrophobic protein, initially infer that it is related to the differentiation of T lymphocytes, and subsequent studies have confirmed that the MAL gene is one of the functional components of the vesicle transport and protein separation between the distal plasma membrane and the Golgi matrix,.MAL is expressed in different kinds of cells, and is indispensable for the normal structure and function of the cells. Several experimental studies have confirmed that the MAL gene is a candidate tumor suppressor gene and is reduced or missing in many tumor cells. The promoter methylation of the promoter may be one of the main mechanisms of gene inactivation and expression deletion. Different studies have confirmed that the methylation of the MAL gene exists in a variety of tumors, but in the epithelial dysplasia of the esophagus. The study of type hyperplasia is rare. Therefore, this paper studies the status of MAL methylation in the process of atypical hyperplasia of the esophagus and whether MAL methylation is a continuous event or some association trend in the development of esophageal carcinogenesis in order to provide a certain reference value for the early diagnosis and screening of esophageal cancer. Objective 1. to study the MAL gene. The methylation and clinical significance of methylation of esophageal squamous cell carcinoma and the degree of methylation of.2.MAL gene are associated with esophageal carcinogenesis. Methods a total of 36 cases of pathological specimens of esophageal squamous cell carcinoma in 2014.10-2015.10 of the First Affiliated Hospital of Zhengzhou University were collected, including cancer tissue and cancer tissue. There were 47 cases of atypical hyperplasia of esophageal epithelium in the pathology department of the First Affiliated Hospital of Zhengzhou University, including 13 cases of mild atypical hyperplasia, 21 cases of moderate atypical hyperplasia, 13 cases of severe dysplasia, and the method of methylation was mainly used in the test. PCR (MSP) technique was used to detect the level of MAL methylation in esophageal squamous cell carcinoma, atypical hyperplasia and its adjacent normal tissues. Statistical methods used chi 2 test and Fisher exact probability method, with P0.05 as the statistical significance and SPSS 20 software. Results the incidence of MAL methylation in 1. esophageal squamous carcinoma tissues was 22 cases (61.1%), and MA in the normal tissue adjacent to the carcinoma. The methylation rate of L gene was 11.1%, the incidence of methylation among the two groups was statistically significant (P0.05) 47 cases of atypical hyperplasia of.2.'s esophagus, 19 cases of methylation of MAL gene, (39.5%), 13 cases of mild atypical hyperplasia, 2 cases of methylation (0%), 0 (0%) (0%) (0%), mild atypical hyperplasia and adjacent lesions. There were 21 cases of moderate atypical hyperplasia, including methylation in 10 cases (47.6%), methylation in 2 paratypical tissues (9.5%), (P0.05), and the two groups were statistically significant; 13 cases of severe atypical hyperplasia, including 7 methylation (53%), 1 cases of methylation (7.6%), (7.6%), and two groups were compared. There was no significant correlation between the methylation level of MAL in.3.ESCC tissue with age, sex, invasion depth, tumor size, lymph node metastasis, tumor staging and other esophageal cancer related clinicopathological factors (P0.05). Conclusion the methylation changes of the 1.MAL gene occur in the light of the esophagus, and in the severe atypical hyperplasia tissue, with the increase of the degree of pathological changes. DNA methylation in.2. esophageal squamous cell carcinoma may be one of the mechanisms of MAL inactivation in the esophageal squamous cell carcinoma. MAL methylation detection may provide a new screening method for the early diagnosis of esophageal cancer, which may provide a new screening method for.3. esophageal squamous cell carcinoma, such as age, sex, and invasion. There was no correlation between depth, tumor size, lymph node metastasis or tumor stage.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.1

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本文編號(hào)：1866709