Abnormal methylation of seven genes and their associations with clinical characteristics in early stage non-small cell lung cancer

Zhao,Yangxing; Zhou,Huafu; Ma,Kelong; Sun,Jinfeng; Feng,Xu; Geng,Junfeng; Gu,Jun; Wang,Wei; Zhang,Hongyu; He,Yinghua; Guo,Shicheng; Zhou,Xiaoyu; Yu,Jian; Lin,Qiang

doi:10.3892/ol.2013.1161

April 2013 Volume 5 Issue 4

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April 2013 Volume 5 Issue 4

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Article

Abnormal methylation of seven genes and their associations with clinical characteristics in early stage non-small cell lung cancer

Authors:
- Yangxing Zhao
- Huafu Zhou
- Kelong Ma
- Jinfeng Sun
- Xu Feng
- Junfeng Geng
- Jun Gu
- Wei Wang
- Hongyu Zhang
- Yinghua He
- Shicheng Guo
- Xiaoyu Zhou
- Jian Yu
- Qiang Lin
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Affiliations: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, P.R. China, Department of Cardiac Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530022, P.R. China, School of Life Science, Anhui Medical University, Hefei 230032, P.R. China, Department of General Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China, Ministry of Education Key Laboratory of Contemporary Anthropology School of Life Sciences, Fudan University, Shanghai 200443, P.R. China, Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, P.R. China
Pages: 1211-1218
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Published online on: January 29, 2013

https://doi.org/10.3892/ol.2013.1161
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Abstract

To identify novel abnormally methylated genes in early stage non-small cell lung cancer (NSCLC), we analyzed the methylation status of 13 genes (ALX1, BCL2, FOXL2, HPP1, MYF6, OC2, PDGFRA, PHOX2A, PITX2, RARB, SIX6, SMPD3 and SOX1) in cancer tissues from 101 cases of stage I NSCLC patients and lung tissues from 30 cases of non-cancerous lung disease controls, using methylation-specific PCR (MSP). The methylation frequencies (29.70-64.36%) of 7 genes (MYF6, SIX6, SOX1, RARB, BCL2, PHOX2A and FOLX2) in stage I NSCLC were significantly higher compared with those in non-cancerous lung disease controls (P<0.05). The co-methylation of SIX6 and SOX1, or the co-methyaltion of SIX6, RARB and SOX1 was associated with adenosquamous carcinoma (ADC), and the co-methylation of BCL2, RARB and SIX6 was associated with smoking. A panel of 4 genes (MYF6, SIX6, BCL2 and RARB) may offer a sensitivity of 93.07% and a specificity of 83.33% in the diagnosis of stage I NSCLC. Furthermore, we also detected the expression of 8 pathological markers (VEGF, HER-2, P53, P21, EGFR, CHGA, SYN and EMA) in cancer tissues of stage I NSCLC by immunohistochemistry, and found that high expression levels of p53 and CHGA were associated with the methylation of BCL2 (P=0.025) and PHOX2A (P=0.023), respectively. In this study, among the 7 genes which demonstrated hypermethylation in stage I NSCLC compared with non-cancerous lung diseases, 5 genes (MYF6, SIX6, PHOX2A, FOLX2 and SOX1) were found for the first time to be abonormally methylated in NSCLC. Further study of these genes shed light on the carcinogenesis of NSCLC.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Abnormal methylation of seven genes and their associations with clinical characteristics in early stage non-small cell lung cancer

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