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Mol. Cells 2012; 34(2): 171-176

Published online August 31, 2012

https://doi.org/10.1007/s10059-012-0083-5

© The Korean Society for Molecular and Cellular Biology

Methylation of TMEFF2 Gene in Tissue and Serum DNA from Patients with Non-Small Cell Lung Cancer

Su Man Lee1, Jae Yong Park2,*, and Dong Sun Kim1,*

1Department of Anatomy, School of Medicine, Kyungpook National University, Daegu 702-422, Korea, 2Internal Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Korea

Correspondence to : *Correspondence: doskim@knu.ac.kr (DSK); jaeyong@knu.ac.kr (JYP)

Received: March 19, 2012; Accepted: May 31, 2012

Abstract

Lung cancer remains a global health problem with a high mortality rate. CpG island methylation is a common aber-ration 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 epige-netically 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 methy-lation 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 detec-ted in the serum of NSCLC patients at a frequency of 9.2% (29/316). These findings suggest that methylation-asso-ciated down-regulation of TMEFF2 gene may be involved in lung tu-morigenesis and TMEFF2 methylation can serve as a specific blood-based biomarker for NSCLC.

Keywords methylation, methylation-specific PCR, non-small cell lung cancer, serum, TMEFF2

Article

Research Article

Mol. Cells 2012; 34(2): 171-176

Published online August 31, 2012 https://doi.org/10.1007/s10059-012-0083-5

Copyright © The Korean Society for Molecular and Cellular Biology.

Methylation of TMEFF2 Gene in Tissue and Serum DNA from Patients with Non-Small Cell Lung Cancer

Su Man Lee1, Jae Yong Park2,*, and Dong Sun Kim1,*

1Department of Anatomy, School of Medicine, Kyungpook National University, Daegu 702-422, Korea, 2Internal Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Korea

Correspondence to:*Correspondence: doskim@knu.ac.kr (DSK); jaeyong@knu.ac.kr (JYP)

Received: March 19, 2012; Accepted: May 31, 2012

Abstract

Lung cancer remains a global health problem with a high mortality rate. CpG island methylation is a common aber-ration 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 epige-netically 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 methy-lation 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 detec-ted in the serum of NSCLC patients at a frequency of 9.2% (29/316). These findings suggest that methylation-asso-ciated down-regulation of TMEFF2 gene may be involved in lung tu-morigenesis and TMEFF2 methylation can serve as a specific blood-based biomarker for NSCLC.

Keywords: methylation, methylation-specific PCR, non-small cell lung cancer, serum, TMEFF2

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
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Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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