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
View Affiliations
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
- Published online on: January 29, 2013 https://doi.org/10.3892/ol.2013.1161
-
Pages:
1211-1218
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
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.
View References
1
|
Molina JR, Yang P, Cassivi SD, Schild SE
and Adjei AA: Non-small cell lung cancer: epidemiology, risk
factors, treatment, and survivorship. Mayo Clin Proc. 83:584–594.
2008. View Article : Google Scholar : PubMed/NCBI
|
2
|
Rauch TA, Wang Z, Wu X, Kernstine KH,
Riggs AD and Pfeifer GP: DNA methylation biomarkers for lung
cancer. Tumour Biol. 33:287–296. 2012. View Article : Google Scholar : PubMed/NCBI
|
3
|
Yu J, Zhu T, Wang Z, et al: A novel set of
DNA methylation markers in urine sediments for sensitive/specific
detection of bladder cancer. Clin Cancer Res. 13:7296–7304. 2007.
View Article : Google Scholar : PubMed/NCBI
|
4
|
Feng Q, Hawes SE, Stern JE, et al: DNA
methylation in tumor and matched normal tissues from non-small cell
lung cancer patients. Cancer Epidemiol Biomarkers Prev. 17:645–654.
2008. View Article : Google Scholar : PubMed/NCBI
|
5
|
Chung JH, Lee HJ, Kim BH, Cho NY and Kang
GH: DNA methylation profile during multistage progression of
pulmonary adenocarcinomas. Virchows Arch. 459:201–211. 2011.
View Article : Google Scholar : PubMed/NCBI
|
6
|
Lin R, Wu C, Chang J, et al: Dysregulation
of p53/Sp1 control leads to DNA methyltransferase-1 overexpression
in lung cancer. Cancer Res. 70:5807–5817. 2010. View Article : Google Scholar : PubMed/NCBI
|
7
|
Mathews LA, Hurt EM, Zhang X and Farrar
WL: Epigenetic regulation of CpG promoter methylation in invasive
prostate cancer cells. Mol Cancer. 9:2672010. View Article : Google Scholar : PubMed/NCBI
|
8
|
Su HY, Lai HC, Lin YW, Chou YC, Liu CY and
Yu MH: An epigenetic marker panel for screening and prognostic
prediction of ovarian cancer. Int J Cancer. 124:387–393. 2009.
View Article : Google Scholar : PubMed/NCBI
|
9
|
Titulaer MJ, Klooster R, Potman M, et al:
SOX antibodies in small-cell lung cancer and Lambert-Eaton
myasthenic syndrome: frequency and relation with survival. J Clin
Oncol. 27:4260–4267. 2009. View Article : Google Scholar : PubMed/NCBI
|
10
|
Benfante R, Antonini RA, Kuster N, et al:
The expression of PHOX2A, PHOX2B and of their target gene
dopamine-beta-hydroxylase (DbetaH) is not modified by exposure to
extremely-low-frequency electromagnetic field (ELF-EMF) in a human
neuronal model. Toxicol In Vitro. 22:1489–1495. 2008. View Article : Google Scholar
|
11
|
Frenzel A, Grespi F, Chmelewskij W and
Villunger A: Bcl2 family proteins in carcinogenesis and the
treatment of cancer. Apoptosis. 14:584–596. 2009. View Article : Google Scholar : PubMed/NCBI
|
12
|
Kelly PN and Strasser A: The role of Bcl-2
and its pro-survival relatives in tumourigenesis and cancer
therapy. Cell Death Differ. 18:1414–1424. 2011. View Article : Google Scholar : PubMed/NCBI
|
13
|
Liu W, Bulgaru A, Haigentz M, Stein CA,
Perez-Soler R and Mani S: The BCL2-family of protein ligands as
cancer drugs: the next generation of therapeutics. Curr Med Chem
Anticancer Agents. 3:217–223. 2003. View Article : Google Scholar : PubMed/NCBI
|
14
|
Vasiljevic N, Wu K, Brentnall AR, et al:
Absolute quantitation of DNA methylation of 28 candidate genes in
prostate cancer using pyrosequencing. Dis Markers. 30:151–161.
2011. View Article : Google Scholar : PubMed/NCBI
|
15
|
Molina R, Alvarez E, Aniel-Quiroga A, et
al: Evaluation of chromogranin A determined by three different
procedures in patients with benign diseases, neuroendocrine tumors
and other malignancies. Tumour Biol. 32:13–22. 2011. View Article : Google Scholar
|
16
|
Ma Z, Tsuchiya N, Yuasa T, et al: Clinical
significance of polymorphism and expression of chromogranin a and
endothelin-1 in prostate cancer. J Urol. 184:1182–1188. 2010.
View Article : Google Scholar : PubMed/NCBI
|