title: Unmethylation of the CHRNB4 gene is an unfavorable prognostic factor in non-small cell lung cancer.
abstract: OBJECTIVE
  Lung cancer is the leading cause of cancer-related deaths and is currently a major health problem owing to difficulties in diagnosis at the early stage of the disease. Changes in DNA methylation status have now been identified as a critical component in the initiation of lung cancer, and the detection of DNA methylation is expected to be an important method for the early diagnosis of lung cancer. Nicotine, the principal tobacco alkaloid, directly contributes to lung carcinogenesis through the activation of nicotinic acetylcholine receptors (nAchRs).
  
  
  METHODS
  To investigate the role of the CHRNB4 gene, which encodes the nAchR β4 subunit that is ubiquitously expressed on lung epithelial cells, we analyzed its methylation status in 266 patients with non-small cell lung cancer (NSCLC) by using methylation-specific polymerase chain reaction and compared it with clinicopathological parameters.
  
  
  CONCLUSIONS
  The frequency of CHRNB4 unmethylation was 13.5% and 8.3% in malignant and nonmalignant tissues, respectively. CHRNB4 demethylation was associated with upregulation of its mRNA expression and was more frequent in squamous cell carcinoma and pathological stages II-IIIA disease than in adenocarcinoma and pathological stage I disease, respectively (P=0.003 and P=0.01, respectively). Univariate and multivariate analyses showed that CHRNB4 unmethylation was significantly associated with unfavorable overall survival in the entire patient group as well as in men and ever-smokers. These results suggest that epigenetic regulation of CHRNB4 may affect tumor progression and survival in patients with NSCLC. Further investigation into the molecular basis of the role of CHRNB4 in the progression of NSCLC is warranted.
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea.
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.affiliation: Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu 702-422, Republic of Korea.
authors.forename: Su Man
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea.
authors.forename: Sook Kyung
authors.initials: SK
authors.lastname: Do
authors.affiliation: Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea.
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.affiliation: Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu 702-422, Republic of Korea. Electronic address: doskim@knu.ac.k.
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea. Electronic address: jaeyong@knu.ac.kr.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics*; D063868:Patient Outcome Assessment; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors
chemical_list: C447159:CHRNB4 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic
keywords: CHRNB4; Methylation-specific polymerase chain reaction; Nicotinic acetylcholine receptors; Non-small cell lung cancer; Prognosis; Unmethylation