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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
Dec 31, 2021 Vol.44 No.12, pp. 861~919
COVER PICTURE
Structure of the fly peripheral neurons in the fly head. Flies have basic sensory organs including eyes for vision, antennae and maxillary palps for olfaction, and proboscis (magenta) for gustation which can be labelled with monoclonal antibody 22C10. The figure is a 3D reconstructed image with 30 slices of confocal sections with 3 μm interval. It shows that the proboscis is required for sensing attractive carboxylic acids such as glycolic acid, citric acid, and lactic acid (Shrestha and Lee, pp. 900-910).

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