Promoter Hypermethylation Of Tumor-related Genes In The Plasma Of Patients With Lung Cancer And Its Significance

Objective:Presently,the morbidity and mortality of lung cancer trends to increasse in the world,and its mortality rate ranks the highest of all the tumors in our country.Earlier detection of lung cancer would facilitate more effective management of the disease.Aberrant methylation of the genes in tumor cells resulted in the epigenetic changes without any alteration of the DNA sequence.Aberrant methylation of promoter CpG islands was known to be a major inactivation mechanism of the tumor suppressor genes and tumor-related genes.Most studies indicated that the promoter hypermethylation of many tumor-related genes existed in the lung cancer,and the promoter hypermethylation of WIF-1,RASSF1A,BLU and CDH13 was associated with the occurrence and the development of lung cancer.Recent evidence showed that the presence of promoter hypermethylation of the tumor-related genes has been demonstrated in the serum or plasma DNA of patients with various cancers such as gastric,liver,and head and neck cancer.This study was designed to detect the methylation status of the promoter region of WIF-1, RASSF1A,BLU and CDH13 gene in plasma DNA from lung cancer,and evaluate the role of the four gene promoter hypermethylation in lung cancer screening and early diagnosis.Methods:Experimental group:58 Plasma samples of lung cancer patients.Control group:20 plasma samples of healthy volunteers.Nested methylation-specific PCR was used to detect the aberrant promoter hypermethylation of WIF-1,RASSF1A,BLU and CDH13 genes in plasma DNA from 58 lung cancer patients,and to analyze the relation of the aberrant methyl ation of the four genes and the clinical pathological data.Results:The positive rates of promoter hypermethylation of WIF-1, RASSF1A,BLU and CDH13 gene were 34.48%(20/58),37.93%(22/58), 29.31%(17/58) and 31.03%(18/58) in the patients with lung cancer.No aberrant promoter methylation was detected in the healthy individuals (P=0.002,0.001,0.006,0.005 respectively).Overall 77.59%of the patients with lung cancer were detected to have promoter hypermethylation at least in one of above genes.Hypermethylation of WIF-1 was more frequent in the patients with smoking(vs non-smoking patients P＜0.05).No correlation was found between the hypermethylation of the four genes and the clinical factors,including the age,sex,TNM stage and pathological classification of the patients.Conclusion:Hypermethylation of WIF-1 was more frequent in the patients with smoking.The detection of WIF-1,RASSF1A,BLU and CDH13 gene promoter hypermethylation in the plasma of lung cancer patients provided useful information for the screening,early diagnosis of lung cancer.