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Promoter hypermethylation of the CFTR gene and clinical/pathological features associated with non‐small cell lung cancer
Author(s) -
SON JI WOONG,
KIM YOUNG JIN,
CHO HYUN MIN,
LEE SOO YOUNG,
LEE SU MAN,
KANG JAEKU,
LEE JUNG UEE,
LEE YU MI,
KWON SUN JUNG,
CHOI EUGENE,
NA MOON JUN,
PARK JAE YONG,
KIM DONG SUN
Publication year - 2011
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2011.01994.x
Subject(s) - methylation , dna methylation , cancer research , lung cancer , cystic fibrosis transmembrane conductance regulator , gene expression , promoter , gene , biology , medicine , microbiology and biotechnology , pathology , genetics
Background and objective: The exact role of the cystic fibrosis transmembrane conductance regulator (CFTR) in pathophysiology, and the mechanisms regulating its expression are poorly understood. The CFTR gene is known to be genetically or epigenetically associated with several cancers. In the present study, the methylation status of the promoter region of the CFTR gene and its expression in primary non‐small cell lung cancer (NSCLC) were investigated. Methods: The methylation status of the promoter region of the CFTR gene in NSCLC tissue was assessed by pyrosequencing and methylation‐specific PCR. Expression of the CFTR gene was analysed by real‐time PCR, and CFTR gene reactivation was investigated using 5‐aza‐2′‐deoxycytidine. The correlation between methylation of the CFTR gene and the clinical features of the patients was assessed. Results: Methylation of the CFTR gene in NSCLC was quantitatively high by pyrosequencing analysis and qualitatively frequent by methylation‐specific PCR analysis. Expression of the CFTR gene was significantly lower in NSCLC compared with normal lung tissue. In addition, the demethylating agent 5‐aza‐2′‐deoxycytidine increased CFTR gene expression. Methylation of the CFTR gene was significantly greater in squamous cell carcinomas than in adenocarcinomas. CFTR gene methylation was associated with significantly poorer survival in young patients, but not in elderly patients. Conclusions: These findings suggest that DNA methylation may be important for downregulation of CFTR gene expression in lung cancer. Promoter hypermethylation of the CFTR gene may be an important prognostic factor in younger patients with NSCLC.