| Esophageal cancer is one of the common malignant tumors that threaten human health.It is the third most common malignant tumor of the digestive tract.Its mortality rate ranks sixth among all malignant tumors.Esophageal cancer can be divided into esophageal squamous cell carcinoma(ESCC)and esophageal gland carcinoma(EAC),and China is a high incidence area of Esophageal cancer,mainly of Squamous Cell Carcinoma.The mortality rate of esophageal cancer is high,the treatment effect is not good.The reason is mainly due to the early asymptomatic or only slight discomfort of esophageal cancer,until the middle and late stages of the development of dysphagia.The short of diagnostic techniques cant cause individuals to miss the best treatment time.Therefore,in-depth understanding of the molecular mechanism of esophageal carcinogenesis,the establishment of molecular indicators and means for early diagnosis is a major issue for esophageal cancer research.At present,the research on the biological indicators of early diagnosis of esophageal cancer,factors that regulate tumor progression,and the methylation of its regulatory genes have been highly concerned by researchers.The epigenetic alteration of tumor suppression gene is one of most significant indicators in human ESCC.In this study,based on the analysis of the Illumina 450 K methylation chip data on the TCGA database site,a candidate site for hypermethylation in ESCC was obtained,and at the same time,we validated the high frequent hypermethylation status of EYA4 promoter regions in 94 Chinese Han ESCC patients and adjacent normal tissues with Target Area Methylated Methyl Target Sequencing.We assessed the sensitivity and specificity of this gene hypermethylation diagnosis of ESCC by Logistic regression.The results showed that the sensitivity was 51%,specificity was 92%,and the area under the ROC curve(AUC)was 0.76.Therefore,EYA4 methylation status has potential clinical application as a biomarker for the early diagnosis of ESCC.Next,we further studied the molecular regulation mechanism of EYA4 in the development of ESCC.The results show:1.The treatment of ESCC cells by in vitro demethylation drug(5-AZA)and dual luciferase reporter system experiments confirmed that the expression of the gene was indeed regulated by methylation modification.2.It was confirmed by DNA Pulldown experiments that Sp1 could bind to EYA4 promoter region,and the methylation of EYA4 promoter region could affect the binding ability of Sp1 and EYA4 promoter region,which resulted in the decrease of EYA4 gene expression.3.By detecting the effect of EYA4 on proliferation,apoptosis,and migration of ESCC cells and their biological behaviors such as tumorigenicity in tumor-bearing mice,EYA4 was elucidated as an anti-oncogene and played an important role in inhibiting tumor cell proliferation,migration and invasion.Significantly promote the apoptosis of tumor cells and inhibit tumor subcutaneous tumor formation in mice.4.The overexpression of EYA4 gene in ESCC cell line affects the expression of p53 m RNA and protein.We speculate that EYA4 exerts its anti-cancer effect through p53 signaling pathway.This part of the experimental study,analysis of the EYA4 gene methylation status can be used as biomarkers for the early diagnosis of ESCC,and provide new ideas and methods for early diagnosis of esophageal squamous cell carcinoma.The preliminary analysis of the mechanism of EYA4 gene expression laid a foundation for further elucidating the molecular mechanism of the gene in the development of ESCC.Based on another research direction: explore the relationship between rs10864907 polymorphism and susceptibility to lung cancer.Lung cancer is the most common malignancy in the world.In many countries in the world,including China,the mortality rate of lung cancer is far higher than that of other malignant tumors,and ranks first in the cause of death of all malignant tumors.Lung cancer is mainly caused by the combination of external factors and genetic factors,and genetic factors are important incentives that affect the occurrence of lung cancer.Since most patients have obvious clinical symptoms,they will seek medical treatment.At this moment,most patients have entered the late stage and miss the best time for treatment.Routine treatment cannot cure lung cancer.Therefore,through early screening and early diagnosis of lung cancer,effective treatment can be conducted in time to reduce the mortality rate of lung cancer patients.Single nucleotide polymorphisms(SNPs)are one of the most important causes of genetic variation in individuals.They are currently one of the most widely used genetic markers in clinical diagnosis and are of great significance for screening of susceptible individuals.We used the rs10864907(C/T)polymorphism site as a research object,and explored the relationship between SNP loci and lung cancer susceptibility in Chinese population through case-control study in 513 lung cancer cases and 783 normal controls.The results showed that the rs10864907(C/T)loci were significantly associated with the genetic susceptibility of lung cancer.The risk of lung cancer in patients with CT genotypes was significantly reduced.By adjusting for age,gender,smoking,and drinking,significance remains.It was shown that CT genotypes significantly reduced the risk of lung cancer(OR=0.74,95% CI;0.58-0.95,P=0.017).This part of the experimental study laid the foundation for further research on the role and function of rs10864907(C/T)loci in the development of lung cancer,providing a theoretical basis for early screening,early diagnosis and early treatment of lung cancer susceptible population. |
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