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

Published online July 18, 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
Feb 28, 2023 Vol.46 No.2, pp. 69~129
COVER PICTURE
The bulk tissue is a heterogeneous mixture of various cell types, which is depicted as a skein of intertwined threads with diverse colors each of which represents a unique cell type. Single-cell omics analysis untangles efficiently the skein according to the color by providing information of molecules at individual cells and interpretation of such information based on different cell types. The molecules that can be profiled at the individual cell by single-cell omics analysis includes DNA (bottom middle), RNA (bottom right), and protein (bottom left). This special issue reviews single-cell technologies and computational methods that have been developed for the single-cell omics analysis and how they have been applied to improve our understanding of the underlying mechanisms of biological and pathological phenomena at the single-cell level.

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