title: Methylation of TMEFF2 gene in tissue and serum DNA from patients with non-small cell lung cancer.
abstract: Lung cancer remains a global health problem with a high mortality rate. CpG island methylation is a common aberration frequently associated with gene silencing in multiple tumor types, emerging as a highly promising biomarker. The transmembrane protein with a single EGF-like and two follistatin domains (TMEFF2) is epigenetically silenced in numerous tumor types, suggesting a potential role as a potential tumor suppressor. However, the role of TMEFF2 in lung cancer remains to be fully elucidated. We explored the methylation status of TMEFF2 gene in 139 patients with non-small cell lung cancer (NSCLC) and the feasibility of detecting circulating methylated DNA as a screening tool for NSCLC using methylation-specific PCR in 316 patients and 50 age-matched health controls. TMEFF2 methylation in tumor tissues was found in 73 of the 139 NSCLCs (52.5%) and was related to gene expression. The frequency of TMEFF2 methylation was higher in females and never-smokers than in males and smokers with borderline significance (65.8% vs 47.8%, p = 0.06; 65.7% vs 48.1%, p = 0.07). Notably, in adenocarcinomas, TMEFF2 methylation was significantly more frequent in tumors without EGFR mutation than those with EGFR mutation (adjusted odds ratio = 7.13, 95% confidence interval = 2.05-24.83, P = 0.002). Furthermore, TMEFF2 methylation was exclusively detected in the serum of NSCLC patients at a frequency of 9.2% (29/316). These findings suggest that methylation-associated down-regulation of TMEFF2 gene may be involved in lung tumorigenesis and TMEFF2 methylation can serve as a specific blood-based biomarker for NSCLC.
authors: Department of Anatomy, School of Medicine, Kyungpook National University, Daegu 702-422, Korea.
authors: Su Man
authors: SM
authors: Lee
authors: Jae Yong
authors: JY
authors: Park
authors: Dong Sun
authors: DS
authors: Kim
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D057890:Epigenomics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D004273:DNA, Neoplasm; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C423567:TMEFF2 protein, human