title: Promoter hypermethylation of the CFTR gene and clinical/pathological features associated with non-small cell lung cancer.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Konyang University Hospital, Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Son
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Cho
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Su Man
authors.initials: SM
authors.lastname: Lee
authors.forename: Jae-Ku
authors.initials: JK
authors.lastname: Kang
authors.forename: Jung Uee
authors.initials: JU
authors.lastname: Lee
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Kwon
authors.forename: Eugene
authors.initials: E
authors.lastname: Choi
authors.forename: Moon Jun
authors.initials: MJ
authors.lastname: Na
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D045744:Cell Line, Tumor; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D056910:Republic of Korea / Q000453:epidemiology
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator