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Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer

  • Authors:
    • Makoto Suzuki
    • Kenji Shiraishi
    • Ayami Eguchi
    • Koei Ikeda
    • Takeshi Mori
    • Kentaro Yoshimoto
    • Yasuomi Ohba
    • Tatsuya Yamada
    • Takaaki Ito
    • Yoshifumi Baba
    • Hideo Baba
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Kumamoto University, Kumamoto 860-8556, Japan, Department of Pathology and Experimental Medicine, Kumamoto University, Kumamoto 860-8556, Japan, Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto 860-8556, Japan
    Copyright: © Suzuki et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1308-1314
    |
    Published online on: January 31, 2013
       https://doi.org/10.3892/or.2013.2266
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Abstract

Genome-wide DNA hypomethylation and gene hypermethylation play important roles in instability and carcino­genesis. Methylation in long interspersed nucleotide element 1 (LINE-1) is a good indicator of the global DNA methylation level within a cell. Slit homolog 2 (SLIT2), myelin and lymphocyte protein gene (MAL) and insulin-like growth factor binding protein 7 (IGFBP7) are known to be hypermethylated in various malignancies. The aim of the present study was to assess the precise methylation levels of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer (NSCLC) using a pyrosequencing assay. Methylation of all regions was examined in 56 primary NSCLCs using a pyrosequencing assay. Changes in mRNA expression levels of SLIT2, MAL and IGFBP7 were measured before and after treatment with a demethylating agent. Methylation of these genes was also examined in 9 lung cancer cell lines using RT-PCR and a pyrosequencing assay. Frequencies of hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7, defined by predetermined cut off values, were 55, 64, 46 and 54% in NSCLCs, respectively and exhibited tumor-specific features. The hypermethylation of all genes was well correlated with changes in expression. The methylation level and frequency of MAL were significantly higher in smokers and in patients without EGFR mutations. Through accurate measurement of methylation levels using pyrosequencing, hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7 were frequently detected in NSCLCs and associated with various clinical features. Analysis of the methylation profiles of these genes may, therefore, provide novel opportunities for the therapy of NSCLCs.
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1 

Takai D and Jones PA: Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci USA. 99:3740–3745. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Suzuki M and Yoshino I: Aberrant methylation in non-small cell lung cancer. Surg Today. 40:602–607. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Gaudet F, Hodgson JG, Eden A, et al: Induction of tumors in mice by genomic hypomethylation. Science. 300:489–492. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Herman JG, Graff JR, Myohanen S, Nelkin BD and Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 93:9821–9826. 1996. View Article : Google Scholar : PubMed/NCBI

5 

Lo YM, Wong IH, Zhang J, Tein MS, Ng MH and Hjelm NM: Quantitative analysis of aberrant p16 methylation using real-time quantitative methylation-specific polymerase chain reaction. Cancer Res. 59:3899–3903. 1999.PubMed/NCBI

6 

Xiong Z and Laird PW: COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res. 25:2532–2534. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Suzuki M, Toyooka S, Shivapurkar N, et al: Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection. Oncogene. 24:1302–1308. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Takahashi T, Shivapurkar N, Riquelme E, et al: Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis. Clin Cancer Res. 10:6126–6133. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Tamura H, Suzuki M, Moriya Y, et al: Aberrant methylation of N-methyl-D-aspartate receptor type 2B (NMDAR2B) in non-small cell carcinoma. BMC Cancer. 11:2202011. View Article : Google Scholar : PubMed/NCBI

10 

Tian L, Suzuki M, Nakajima T, et al: Clinical significance of aberrant methylation of prostaglandin E receptor 2 (PTGER2) in nonsmall cell lung cancer: association with prognosis, PTGER2 expression, and epidermal growth factor receptor mutation. Cancer. 113:1396–1403. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Ronaghi M: Pyrosequencing sheds light on DNA sequencing. Genome Res. 11:3–11. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Sepulveda AR, Jones D, Ogino S, et al: CpG methylation analysis - current status of clinical assays and potential applications in molecular diagnostics: a report of the Association for Molecular Pathology. J Mol Diagn. 11:266–278. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Iwagami S, Baba Y, Watanabe M, et al: Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma. Ann Surg Oncol. 19:2726–2732. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Yamaji H, Iizasa T, Koh E, et al: Correlation between interleukin 6 production and tumor proliferation in non-small cell lung cancer. Cancer Immunol Immunother. 53:786–792. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Suzuki M, Sunaga N, Shames DS, Toyooka S, Gazdar AF and Minna JD: RNA interference-mediated knockdown of DNA methyltransferase 1 leads to promoter demethylation and gene re-expression in human lung and breast cancer cells. Cancer Res. 64:3137–3143. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Baba Y, Huttenhower C, Nosho K, et al: Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors. Mol Cancer. 9:1252010. View Article : Google Scholar : PubMed/NCBI

17 

Yoshida K, Yatabe Y, Park JY, et al: Prospective validation for prediction of gefitinib sensitivity by epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer. J Thorac Oncol. 2:22–28. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Moses LE, Shapiro D and Littenberg B: Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 12:1293–1316. 1993. View Article : Google Scholar : PubMed/NCBI

19 

Saito K, Kawakami K, Matsumoto I, Oda M, Watanabe G and Minamoto T: Long interspersed nuclear element 1 hypomethylation is a marker of poor prognosis in stage IA non-small cell lung cancer. Clin Cancer Res. 16:2418–2426. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Dallol A, Da Silva NF, Viacava P, et al: SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers. Cancer Res. 62:5874–5880. 2002.

21 

Kwon YJ, Lee SJ, Koh JS, et al: Genome-wide analysis of DNA methylation and the gene expression change in lung cancer. J Thorac Oncol. 7:20–33. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Suzuki M, Wada H, Yoshino M, et al: Molecular characterization of chronic obstructive pulmonary disease-related non-small cell lung cancer through aberrant methylation and alterations of EGFR signaling. Ann Surg Oncol. 17:878–888. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Puertollano R, Martin-Belmonte F, Millan J, et al: The MAL proteolipid is necessary for normal apical transport and accurate sorting of the influenza virus hemagglutinin in Madin-Darby canine kidney cells. J Cell Biol. 145:141–151. 1999. View Article : Google Scholar

24 

Mimori K, Shiraishi T, Mashino K, et al: MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway. Oncogene. 22:3463–3471. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Lind GE, Ahlquist T, Kolberg M, et al: Hypermethylated MAL gene - a silent marker of early colon tumorigenesis. J Transl Med. 6:132008. View Article : Google Scholar : PubMed/NCBI

26 

Buffart TE, Overmeer RM, Steenbergen RD, et al: MAL promoter hypermethylation as a novel prognostic marker in gastric cancer. Br J Cancer. 99:1802–1807. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Overmeer RM, Henken FE, Bierkens M, et al: Repression of MAL tumour suppressor activity by promoter methylation during cervical carcinogenesis. J Pathol. 219:327–336. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Ruan W, Xu E, Xu F, et al: IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis. Cancer Biol Ther. 6:354–359. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Vizioli MG, Sensi M, Miranda C, et al: IGFBP7: an oncosuppressor gene in thyroid carcinogenesis. Oncogene. 29:3835–3844. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Mutaguchi K, Yasumoto H, Mita K, et al: Restoration of insulin-like growth factor binding protein-related protein 1 has a tumor-suppressive activity through induction of apoptosis in human prostate cancer. Cancer Res. 63:7717–7723. 2003.

31 

Smith P, Nicholson LJ, Syed N, et al: Epigenetic inactivation implies independent functions for insulin-like growth factor binding protein (IGFBP)-related protein 1 and the related IGFBPL1 in inhibiting breast cancer phenotypes. Clin Cancer Res. 13:4061–4068. 2007. View Article : Google Scholar

32 

Ye F, Chen Y, Knosel T, et al: Decreased expression of insulin-like growth factor binding protein 7 in human colorectal carcinoma is related to DNA methylation. J Cancer Res Clin Oncol. 133:305–314. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Chen Y, Cui T, Knosel T, Yang L, Zoller K and Petersen I: IGFBP7 is a p53 target gene inactivated in human lung cancer by DNA hypermethylation. Lung Cancer. 73:38–44. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Suzuki M, Shiraishi K, Eguchi A, Ikeda K, Mori T, Yoshimoto K, Ohba Y, Yamada T, Ito T, Baba Y, Baba Y, et al: Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer. Oncol Rep 29: 1308-1314, 2013.
APA
Suzuki, M., Shiraishi, K., Eguchi, A., Ikeda, K., Mori, T., Yoshimoto, K. ... Baba, H. (2013). Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer. Oncology Reports, 29, 1308-1314. https://doi.org/10.3892/or.2013.2266
MLA
Suzuki, M., Shiraishi, K., Eguchi, A., Ikeda, K., Mori, T., Yoshimoto, K., Ohba, Y., Yamada, T., Ito, T., Baba, Y., Baba, H."Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer". Oncology Reports 29.4 (2013): 1308-1314.
Chicago
Suzuki, M., Shiraishi, K., Eguchi, A., Ikeda, K., Mori, T., Yoshimoto, K., Ohba, Y., Yamada, T., Ito, T., Baba, Y., Baba, H."Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer". Oncology Reports 29, no. 4 (2013): 1308-1314. https://doi.org/10.3892/or.2013.2266
Copy and paste a formatted citation
x
Spandidos Publications style
Suzuki M, Shiraishi K, Eguchi A, Ikeda K, Mori T, Yoshimoto K, Ohba Y, Yamada T, Ito T, Baba Y, Baba Y, et al: Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer. Oncol Rep 29: 1308-1314, 2013.
APA
Suzuki, M., Shiraishi, K., Eguchi, A., Ikeda, K., Mori, T., Yoshimoto, K. ... Baba, H. (2013). Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer. Oncology Reports, 29, 1308-1314. https://doi.org/10.3892/or.2013.2266
MLA
Suzuki, M., Shiraishi, K., Eguchi, A., Ikeda, K., Mori, T., Yoshimoto, K., Ohba, Y., Yamada, T., Ito, T., Baba, Y., Baba, H."Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer". Oncology Reports 29.4 (2013): 1308-1314.
Chicago
Suzuki, M., Shiraishi, K., Eguchi, A., Ikeda, K., Mori, T., Yoshimoto, K., Ohba, Y., Yamada, T., Ito, T., Baba, Y., Baba, H."Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer". Oncology Reports 29, no. 4 (2013): 1308-1314. https://doi.org/10.3892/or.2013.2266
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