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Journal of Molecular Biomarkers & Diagnosis
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Research Article

Selection of Sensitive Methylation Markers for the Detection of Non-small Cell Lung Cancer

Xia Zhao1*, Jin Jen1, Tobias Peikert2, Eric Edell2, Shulan Tian3, Ping Yang4, Yajue Huang5 and Hongzhi Zou1*

1Division of Experiemental Pathology and Laboratory Medicine, Mayo Clinic, Minnesota, USA

2Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Minnesota, USA

3Division of Biomedical Statistics and Informatics, Mayo Clinic, Minnesota, USA

4Division of Epidemiology, Mayo Clinic, Minnesota, USA

5Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA

*Corresponding Authors:
Hongzhi Zou
Department of Laboratory Medicine and Pathology
Mayo Clinic, 200 First Street SW
Rochester, Minnesota 55905, USA
Tel: +01 507-293-2464
[email protected]
Xia Zhao
Department of Laboratory Medicine and Pathology
Mayo Clinic, 200 First Street SW
Rochester, Minnesota 55905, USA
Tel: +01 507-538- 7547
[email protected]

Received Date: August 06, 2015; Accepted Date: October 02, 2015; Published Date: October 04, 2015

Citation: Zhao X, Jen J, Peikert T, Edell E, Tian S, et al. (2015) Selection of Sensitive Methylation Markers for the Detection of Non-small Cell Lung Cancer. J Mol Biomark Diagn 6:250. doi:10.4172/2155-9929.1000250

Copyright: © 2015 Zhao X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited



Introduction: While early-stage lung cancer is curable by surgical resection, most patients are diagnosed with advanced- stage disease. Annual low-dose computed tomography screening decreases lung cancer mortality, however effective biomarkers to address the high false positive rate and to better define high risk individuals are lacking. This study was designed to identify potential DNA methylation markers for the detection of non-small cell lung cancer, the most common type of lung cancer.

Methods: 152 candidate methylation genes were first investigated in lung cancer cell lines and a pilot set of lung tissues. Five promising methylated genes, DMRTA, HOXA9, ZIC4, HOXA7, and SIX3, were selected and further validated in 150 non-small cell lung cancers and 142 tumor-free surrounding lung tissues using the quantitative methylation-specific PCR.

Results: Methylation levels of DMRTA2, HOXA9, ZIC4, HOXA7, and SIX3 were significantly higher in tumors compared to tumor-free surrounding lung tissues (P<2.2e-16 for all). Receiver operation curve analysis showed that methylation of DMRTA2, HOXA9, ZIC4, HOXA7, and SIX3 identified 93%, 91%, 89%, 81%, and 59% of non-small cell lung cancers (n=150) with a specificity of 95%. Comparing tumors to tumor-free surrounding lung tissues, area under the curve values were 0.967, 0.955, 0.950, 0.904, and 0.819, respectively. The predicted area under the curve value after combining DMRTA2 and HOXA9 was 0.971. Methylation levels of these genes were not correlated to cancer stages (P>0.05).

Conclusion: We identified a group of highly sensitive and specific methylation markers in non-small cell lung cancer. These markers are potential valuable candidates to improve the performance of lung cancer screening.


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