MAL甲基化在食管鳞癌和癌前病变中的研究及临床意义

发布时间：2018-05-09 16:23

本文选题：MAL基因 + 食管鳞状细胞癌　；参考：《郑州大学》2017年硕士论文

【摘要】：研究背景食管癌是常见的一种恶性肿瘤,我国是食管癌高发区,并且发病率和病死率居世界首位。常见的病理类型有食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)和食管腺癌(esophageal adenocarcinoma,EAC),在我国以前者多见,约占90%以上,后者较少见,占10%左右。食管鳞状细胞上皮重度不典型增生作为食管鳞癌癌前病变,是食管正常组织到恶变的一个重要过渡阶段。食管癌的发生是多种因素参与、多阶段、多步骤发展的复杂过程,其发生及发展主要与癌基因过度表达及抑癌基因失活有关。现代肿瘤学认为基因的改变主要涉及两方面:遗传学的改变和表观遗传学的异常;近年多种研究发现表观遗传学的异常改变在肿瘤的发生发展中起到非常重要的作用。表观遗传学是研究基因表达的学科,它是指基因表达的改变不依赖DNA序列的变化,其异常可导致基因的表达沉默和缺失,而其中以DNA甲基化为研究最多的表观遗传调控形式之一[1];MAL基因位于人染色体2q13,它最早由Alonso等[2]于1987发现的一个在T细胞分化中晚期时表达的基因,该基因编码一种高度疏水蛋白,最初推断它与T淋巴细胞分化成熟有关,后续研究证实MAL基因是远端质膜和高尔基体之间囊泡转运和蛋白质分选的作用成分之一。MAL在机体不同种类的细胞中均有表达,对于细胞的正常结构和功能有不可或缺的作用。多项试验研究证实MAL基因是一种候选的抑癌基因,并在很多肿瘤细胞中的表达减少或缺失,其启动子高度甲基化可能是基因失活和表达缺失的主要机制之一。不同的研究证实MAL基因甲基化存在于多种肿瘤中,但在食管黏膜上皮不典型增生中的研究少见,因此本文研究食管不典型增生过程中的MAL甲基化状态,及探讨MAL甲基化在食管癌变发生发展中是否为一连续事件或有某种关联性趋势,以期对食管癌的早期诊断和筛查会提供一定的参考价值。目的1.研究MAL基因在食管鳞状上皮细胞不典型增生、食管鳞状细胞癌的甲基化状态及临床意义。2.MAL基因甲基化程度与食管癌变是否有关联。方法随机收集郑州大学第一附属医院2014.10-2015.10年间食管鳞癌患者术后组织病理标本共36例,其中包括癌组织及癌旁正常组织,其术前均未接受化疗和放疗等治疗;另随机收集郑州大学第一附属医院病理科食管粘膜上皮不典型增生组织标本共47例,其中轻度不典型增生13例,中度不典型增生21例,重度不典型增生13例;试验方法主要使用甲基化特异性PCR(MSP)技术检测食管鳞癌、不典型增生及其对应旁正常组织中MAL甲基化水平。统计学方法采用χ2检验和Fisher确切概率法,以p0.05为有统计学意义,由SPSS 20.0软件完成。结果1.食管鳞癌组织中MAL甲基化发生率为22例(61.1%),癌旁正常组织中MAL基因甲基化率为11.1%,两组之间的甲基化发生率比较有统计学意义(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%);其中轻度不典型增生13例,发生甲基化2例(15.4%),病变旁正常组织0例(0%)(p0.05),轻度不典型增生与对应病变旁组织比较无差异;中度不典型增生21例,其中发生甲基化10例(47.6%),病变旁组织2例发生甲基化(9.5%),(p0.05),两组比较有统计学意义;重度不典型增生共13例,其中发生甲基化7例(53.0%),病变旁正常组织1例发生甲基化(7.6%),(p0.05),两组相比较有统计学意义。3.ESCC组织中MAL的甲基化水平与年龄、性别、侵袭深度、肿瘤大小、淋巴结转移、肿瘤分期等食管癌相关临床病理因素无显著相关性(p0.05)。结论1.MAL基因甲基化改变发生于食管的轻、中和重度不典型增生组织,随病变程度的增加,基因的甲基化频率呈逐渐升高趋势。2.食管鳞癌中DNA甲基化可能为MAL基因失活的机制之一,MAL甲基化检测可能为今后食管癌早期辅助诊断提供一种新的筛查检测方法。3.食管鳞癌中MAL基因甲基化频率与相关病理因素,如年龄、性别、侵润深度、肿瘤大小、淋巴结有无转移、肿瘤分期无相关性。
[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.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.1

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