The Methylation Status Of TMS1 Gene In Non-small Cell Lung Cancer And Its Clinical Significance

Background Lung cancer is one of the most common malignant tumors in the world, and is the result of many factors,many stages and many abnormal genes.The reasons lead to abnormal genes include mutation of genes,loss of genes,and epigenetic change of genes.Along with the deeper study of molecular biology mechanisms of tumor,the role of methylation of promoter region which is one format of epigenetics in tumorigenesis attracts more and more attention.In normal cells,the CpG islands of prmoter region are unmethylated,and the CpG bionucleotides distributed dispersally are allways methylated.However,in tumor cells,the total methylation level is lower than normal cells,but it comes accompanied by higher methylation level of some CpG islands.As the CpG islands become methylated,the corresponding genes lose the ability to express.So,it is thought that the change of methylation status of DNA is one way for anti-oncogenes to become inactiviated,and is a key factor to cause tumor. TMS1 is a new pro-apoptosis gene abstracted and identified by Masumoto and Conway when they studyed leukemia and breast tumor respectively.TMS1 can trigger apoptosis by caspase mediating,anti-tumor immunity,and inhibiting the activiation of NF-κB.It is the first gene to be identified in a functional screen for such methylation-induced gene silencing events,and it has been reported be methylated in many malignant tumors.Objective This study was designed to detect the methylation status and protein expression of TMS1 in non-small cell lung cancer and corresponding nomalignant tissues,and analyse the relationship of TMS1 with various clinicopathological character such as tumor's histological type,TNM stage,and the relationship of methylation status with protein expression of TMS1.Methods We abstract DNA from lung tissues,than modify it with sodium bisulfite, purify it,and amplify it with methylated and unmethylated primer at last to detect the methylation status of TMS1 in 50 non-small cell lung cancer tissues and 50 corresponding nomalignant tissues.We also use avidin-biotin-peroxidase complex method to detect the protein expression of TMS1 in those tissues.Results 20 of 50 non-small cell lung cancer tissues have been tested the methylation of TMS1 gene,the frequence is 40%,and there was no methylation tested in any corresponding nomalignant tissue(P＜0.05).The protein expression of TMS1 was decreased in 72%(36/50) of malignant tissues,but was expressed totally in all corresponding nomalignant tissues,none of them was decreased(P＜0.05).There was no correlation of the methylation status or protein expression of TMS1 with patients' gender,smoking,tumor's histological type and TNM stage(P＞0.05).However,the methylation status of TMS1 gene was closely correlated with protein expression (P＜0.05 ).Conclusions The methylation of promotor region of TMS1 gene is a common event in non-small cell lung cancer,and is correlated with the down-regulation of protin expression.The methylation of TMS1 gene plays an important role in tumorigenesis of non-small cell lung cancer.