Expression Level Of Methylation Susceptibility Genes In Esophageal Squamous Carcinoma Of Kazakhs And Its Clinical Significance

Objective: The types of hypermethylated genes in esophageal cancer cells are significantly different in different geographical regions and ethnic groups,which reflects the genetic susceptibility of the population to the disease.The purpose of this study is to investigate the expression level and clinical significance of methylation susceptibility gene in esophageal squamous carcinoma of Kazakh nationality.Methods: Sixteen candidate genes for specific hypermethylation of esophageal cancer were selected by literature retrieval,and the candidate gene CpG islands were predicted by Methyl Primer software.The results of esophageal squamous cancer expression profile microarray of Kazakhs were analyzed by secondary biological information analysis to screen differentially expressed genes.The differentially expressed genes and specific hypermethylated candidate genes of esophageal squamous cancer were cross-analyzed by human genome-wide oligonucleotide microarray to determine the methylated susceptibility genes of Kazakhs,qRT-PCR and immunohistochemistry(IHC)were then used to detect the expression of susceptible genes in esophageal squamous cancer and para-carcinoma tissues of Kazakhs and to analyze the relationship with clinical characteristics and survival rate.Results: 16 candidate genes were predicted by methylated CpG islands,cross-analysis of differentially expressed genes in Kazakhs esophageal squamous cancer expression chips,and the bioinformatics analysis of the relationship between TCGA database query expression levels and prognostic,etc.,finally selected 5 genes including PTEN,FHIT,CLDN3,MLH1 and MSH2,qRT-PCR results showed that the mRNA expression levels of hMSH2 A and FHIT genes in esophageal squamous cell carcinoma tissues both were significantly higher than that in para-carcinoma tissues,both of which were highly expressed in para-carcinomatissues and low in cancer tissues.After statistical analysis,it was found that the low expression of hMSH2 A and FHIT genes had not relationthip with the age,sex and tumor location of esophageal cancer patients;HMSH2A gene was related to the degree of differentiation(P=0.020)was related to the lymph node metastasis in TNM stage(P=0.028)and pathological stage(P=0.014),FHIT gene expression is related to the depth of tumor TNM stage infiltration(P=0.031),Kaplan-meier survival analysis found that the survival rate and survival time of hMSH2 A gene expression positive patients in cancer tissues were better than those with negative gene expression.The co-expression of the two genes in carcinoma and para-carcinoma tissues suggested that hMSH2 A expression was positively correlated with FHIT expression(r=0.430,P<0.01).Conclusion: Methylated susceptibility genes hMSH2 A and FHIT may play an important role in the occurrence and development of esophageal squamous cancer in Kazakhs people.The detection of the combined expression of the two genes can be used as an important indicator to predict the malignant phenotype and prognosis.