| Background Esophageal cancer is one of the most common malignant tumors in our country,and China is a high incidence area of esophageal cancer.The common pathological types of esophageal cancer are esophageal adenocarcinoma(esophageal adenocarcinoma EAC)and esophageal squamous cell carcinoma(esophageal squamous cell carcinoma ESCC).Squamous cell carcinoma is largely common while adenocarcinoma is rare in China.Esophageal epithelial dysplasia as a precancerous lesion of esophageal squamous carcinoma,is a slow transition stage from esophageal normal tissues to the malignant transformation.The occurrence of esophageal cancer is a process of multiple factors participation,multi-step development,and its occurrence and development is mainly related to overexpression of oncogenes and inactivation of tumor suppressor genes.Oncology gene changes mainly involves two aspects: abnormal genetic and epigenetic changes.Recent studies have found that epigenetic abnormalities play a very important role in the development of tumers Epigenetics is a subject which is the study of gene expression and refers to changes in gene expression while not dependent on DNA sequence,and its abnormality may lead to silencing and gene deletion,with DNA methylation being the most studied epigenetic regulation [1];MAL gene is located at 2q13 in human chromosome,which is the earliest found by Alonso [2] in the expression of T cell differentiation in 1987 and encoding a highly hydrophobic protein,initially considering that it is relevant to T lymphocyte differentiation,follow-up study confirmed that the MAL gene is vesicle trafficking and protein separation effect between the distal component of plasma membrane and Golgi apparatus,and expressed in different cell types in the body,haveing an essential role for the normal structure and function of cells.Many experiments showed that MAL gene was reduced and absent in many tumor cells,and the promoter hypermethylation may be the main mechanism of gene inactivation and deletion of expression.Recent studies found that MAL gene is a candidate tumor suppressor gene.At the same time a number of studies have confirmed the methylation of MAL gene exists in a variety of tumors,but in esophageal atypical hyperplasia of is rare.So by studying whether the existence of MAL gene methylation in the process from esophageal atypical hyperplasia to carcinoma,and investigating relationship of the methylation of MAL gene and the occurrence of esophageal cancer and development,we hope it will benefit in early diagnosis and screening in esophageal cancer and provides a certain reference clinical value.Objective1.To study the methylation status of MAL gene in esophageal precancerous lesion and esophageal squamous cell carcinoma and its clinical significance.2.Whether the degree of methylation of MAL gene is associated with esophageal carcinogenesis.Methods Samples were collected from the First Affiliated Hospital of Zhengzhou University during the period of 2014.10-2015.10 in patients with esophageal squamous cell carcinoma and the specimens of postoperative pathological were 36 cases,including carcinoma tissue and normal tissue,which were not receiving preoperative chemotherapy and radiation therapy;Another collection of the pathology of esophageal mucous membrane atypical hyperplasia tissuesthe in the First Affiliated Hospital of Zhengzhou University Department of were 47 cases,including mild 13 cases of atypical hyperplasia,21 cases of moderate dysplasia,severe dysplasia in 13 cases;Use methylation specific PCR technique to detect the methylation status of MAL gene in esophageal carcinoma and atypical hyperplasia of esophageal lesions in the adjacent tissues.Statistical analysis was performed by C2 test and Fisher exact probability method,and p<0.05 was statistically significant,which was completed by SPSS 20.0 software.Results 1.The methylation rate of MAL gene in esophageal squamous cell carcinoma was 22 cases(61.1%),and the methylation rate of MAL gene in the adjacent tissues was 11.1%.There was a significant difference in the incidence of MAL gene methylation between esophageal squamous cell carcinoma and adjacent tissues(p<0.05).2.Esophageal epithelial dysplasia is a total of 47 cases,MAL gene methylation is 17 cases,accounting for 36%.Mild dysplasia occurred in 2 cases(15.4%),and adjacent normal tissues(0%)(0);There were 10(n = 47.6%)cases occurred methylation in moderate atypical hyperplasia,and the adjacent tissues 2cases was observed in all the patients(p<0.05),and there was statistical significance between the two groups;There were 7(n=53%)cases occurred methylation in severe atypical hyperplasia,and normal tissues(n = 7.6%),there was statistical significance between the two groups.3.The methylation frequency of MAL in ESCC was not significantly different in tumor size,invasion depth and lymph node metastasis.(p>0.05).Conclusions 1.The methylation of MAL gene was found in the mild,moderate and severe dysplasia of the esophagus.The stage of esophageal squamous dysplasia,with increasing severity and frequency of gene methylation increased gradually 2.The results suggest that MAL methylation detection can be used in early diagnosis of esophageal carcinoma and is the possible mechanism of DNA methylation inactivation of MAL gene in esophageal squamous cell carcinoma.3.the frequency of methylation of MAL in ESCC was not correlated with tumor size,depth of invasion,and lymph node metastasis. |
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