Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma

Shinji Kikuchi, Daisuke Yamada, Takeshi Fukami, Tomoko Maruyama, Akihiko Ito, Hisao Asamura, Yoshihiro Matsuno, Masataka Onizuka, Yoshinori Murakami

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Abstract

BACKGROUND. The tumor suppressor gene TSLC1/IGSF4 on chromosomal region 11q23 is frequently inactivated by promoter methylation in various cancers, including nonsmall cell lung carcinoma (NSCLC). Several studies have demonstrated that the hypermethylation of the CpG islands of genes, including tumor suppressors, is associated with exposure to tobacco smoke. The purpose of this study was to investigate the possible association of TSLC1/IGSF4 methylation with tobacco smoking as well as with the clinical characteristics of tumors using a large number of primary NSCLC. METHODS. The promoter methylation of TSLC1/IGSF4 was analyzed in 103 primary NSCLC. TSLC1/IGSF4 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, whereas its methylation status was determined by bisulfite single-strand conformation polymorphism (SSCP) coupled with bisulfite sequencing. RESULTS. The TSLC1/IGSF4 promoter was methylated in 45 (44%) of 103 primary NSCLC. Methylation was observed in all histologic subtypes of NSCLC, including adenocarcinoma (29 of 68, 43%), squamous cell carcinoma (14 of 26, 54%), adenosquamous carcinoma (1 of 2, 50%), and large cell carcinoma (1 of 7, 14%). The incidence of methylation in tumors was significantly higher in male patients than in female patients (P = .027). The TSLC1/IGSF4 methylation was preferentially observed in heavy smokers (smoking index a 800) (P = .0054). Furthermore, in smokers the methylation was significantly associated with pack-years smoked (P = .034) and cigarettes per day (P = .021). The TSLC1/IGSF4 methylation was also significantly associated with a shorter disease-free survival (P = .049), providing an independent prognostic factor (P = .038) in adenocarcinoma patients. CONCLUSIONS. TSLC1/IGSF4 methylation is associated with tobacco smoking and could be an indicator of poor prognosis.

Original languageEnglish
Pages (from-to)1751-1758
Number of pages8
JournalCancer
Volume106
Issue number8
DOIs
Publication statusPublished - 2006 May 15
Externally publishedYes

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Methylation
Smoking
Carcinoma
Lung
Tumor Suppressor Genes
Adenocarcinoma
Adenosquamous Carcinoma
Large Cell Carcinoma
CpG Islands
Non-Small Cell Lung Carcinoma
Smoke
Tobacco Products
Reverse Transcription
Disease-Free Survival
Tobacco
Squamous Cell Carcinoma
Neoplasms
Immunohistochemistry
Polymerase Chain Reaction
Incidence

Keywords

  • Bisulfite single-strand conformational polymorphism
  • DAL-1/4.1B gene
  • Nonsmall cell lung carcinoma
  • Prognosis
  • Promoter methylation
  • Tobacco smoking
  • TSLC1/IGSF4 gene

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma. / Kikuchi, Shinji; Yamada, Daisuke; Fukami, Takeshi; Maruyama, Tomoko; Ito, Akihiko; Asamura, Hisao; Matsuno, Yoshihiro; Onizuka, Masataka; Murakami, Yoshinori.

In: Cancer, Vol. 106, No. 8, 15.05.2006, p. 1751-1758.

Research output: Contribution to journalArticle

Kikuchi, S, Yamada, D, Fukami, T, Maruyama, T, Ito, A, Asamura, H, Matsuno, Y, Onizuka, M & Murakami, Y 2006, 'Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma', Cancer, vol. 106, no. 8, pp. 1751-1758. https://doi.org/10.1002/cncr.21800
Kikuchi, Shinji ; Yamada, Daisuke ; Fukami, Takeshi ; Maruyama, Tomoko ; Ito, Akihiko ; Asamura, Hisao ; Matsuno, Yoshihiro ; Onizuka, Masataka ; Murakami, Yoshinori. / Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma. In: Cancer. 2006 ; Vol. 106, No. 8. pp. 1751-1758.
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abstract = "BACKGROUND. The tumor suppressor gene TSLC1/IGSF4 on chromosomal region 11q23 is frequently inactivated by promoter methylation in various cancers, including nonsmall cell lung carcinoma (NSCLC). Several studies have demonstrated that the hypermethylation of the CpG islands of genes, including tumor suppressors, is associated with exposure to tobacco smoke. The purpose of this study was to investigate the possible association of TSLC1/IGSF4 methylation with tobacco smoking as well as with the clinical characteristics of tumors using a large number of primary NSCLC. METHODS. The promoter methylation of TSLC1/IGSF4 was analyzed in 103 primary NSCLC. TSLC1/IGSF4 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, whereas its methylation status was determined by bisulfite single-strand conformation polymorphism (SSCP) coupled with bisulfite sequencing. RESULTS. The TSLC1/IGSF4 promoter was methylated in 45 (44{\%}) of 103 primary NSCLC. Methylation was observed in all histologic subtypes of NSCLC, including adenocarcinoma (29 of 68, 43{\%}), squamous cell carcinoma (14 of 26, 54{\%}), adenosquamous carcinoma (1 of 2, 50{\%}), and large cell carcinoma (1 of 7, 14{\%}). The incidence of methylation in tumors was significantly higher in male patients than in female patients (P = .027). The TSLC1/IGSF4 methylation was preferentially observed in heavy smokers (smoking index a 800) (P = .0054). Furthermore, in smokers the methylation was significantly associated with pack-years smoked (P = .034) and cigarettes per day (P = .021). The TSLC1/IGSF4 methylation was also significantly associated with a shorter disease-free survival (P = .049), providing an independent prognostic factor (P = .038) in adenocarcinoma patients. CONCLUSIONS. TSLC1/IGSF4 methylation is associated with tobacco smoking and could be an indicator of poor prognosis.",
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T1 - Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma

AU - Kikuchi, Shinji

AU - Yamada, Daisuke

AU - Fukami, Takeshi

AU - Maruyama, Tomoko

AU - Ito, Akihiko

AU - Asamura, Hisao

AU - Matsuno, Yoshihiro

AU - Onizuka, Masataka

AU - Murakami, Yoshinori

PY - 2006/5/15

Y1 - 2006/5/15

N2 - BACKGROUND. The tumor suppressor gene TSLC1/IGSF4 on chromosomal region 11q23 is frequently inactivated by promoter methylation in various cancers, including nonsmall cell lung carcinoma (NSCLC). Several studies have demonstrated that the hypermethylation of the CpG islands of genes, including tumor suppressors, is associated with exposure to tobacco smoke. The purpose of this study was to investigate the possible association of TSLC1/IGSF4 methylation with tobacco smoking as well as with the clinical characteristics of tumors using a large number of primary NSCLC. METHODS. The promoter methylation of TSLC1/IGSF4 was analyzed in 103 primary NSCLC. TSLC1/IGSF4 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, whereas its methylation status was determined by bisulfite single-strand conformation polymorphism (SSCP) coupled with bisulfite sequencing. RESULTS. The TSLC1/IGSF4 promoter was methylated in 45 (44%) of 103 primary NSCLC. Methylation was observed in all histologic subtypes of NSCLC, including adenocarcinoma (29 of 68, 43%), squamous cell carcinoma (14 of 26, 54%), adenosquamous carcinoma (1 of 2, 50%), and large cell carcinoma (1 of 7, 14%). The incidence of methylation in tumors was significantly higher in male patients than in female patients (P = .027). The TSLC1/IGSF4 methylation was preferentially observed in heavy smokers (smoking index a 800) (P = .0054). Furthermore, in smokers the methylation was significantly associated with pack-years smoked (P = .034) and cigarettes per day (P = .021). The TSLC1/IGSF4 methylation was also significantly associated with a shorter disease-free survival (P = .049), providing an independent prognostic factor (P = .038) in adenocarcinoma patients. CONCLUSIONS. TSLC1/IGSF4 methylation is associated with tobacco smoking and could be an indicator of poor prognosis.

AB - BACKGROUND. The tumor suppressor gene TSLC1/IGSF4 on chromosomal region 11q23 is frequently inactivated by promoter methylation in various cancers, including nonsmall cell lung carcinoma (NSCLC). Several studies have demonstrated that the hypermethylation of the CpG islands of genes, including tumor suppressors, is associated with exposure to tobacco smoke. The purpose of this study was to investigate the possible association of TSLC1/IGSF4 methylation with tobacco smoking as well as with the clinical characteristics of tumors using a large number of primary NSCLC. METHODS. The promoter methylation of TSLC1/IGSF4 was analyzed in 103 primary NSCLC. TSLC1/IGSF4 expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, whereas its methylation status was determined by bisulfite single-strand conformation polymorphism (SSCP) coupled with bisulfite sequencing. RESULTS. The TSLC1/IGSF4 promoter was methylated in 45 (44%) of 103 primary NSCLC. Methylation was observed in all histologic subtypes of NSCLC, including adenocarcinoma (29 of 68, 43%), squamous cell carcinoma (14 of 26, 54%), adenosquamous carcinoma (1 of 2, 50%), and large cell carcinoma (1 of 7, 14%). The incidence of methylation in tumors was significantly higher in male patients than in female patients (P = .027). The TSLC1/IGSF4 methylation was preferentially observed in heavy smokers (smoking index a 800) (P = .0054). Furthermore, in smokers the methylation was significantly associated with pack-years smoked (P = .034) and cigarettes per day (P = .021). The TSLC1/IGSF4 methylation was also significantly associated with a shorter disease-free survival (P = .049), providing an independent prognostic factor (P = .038) in adenocarcinoma patients. CONCLUSIONS. TSLC1/IGSF4 methylation is associated with tobacco smoking and could be an indicator of poor prognosis.

KW - Bisulfite single-strand conformational polymorphism

KW - DAL-1/4.1B gene

KW - Nonsmall cell lung carcinoma

KW - Prognosis

KW - Promoter methylation

KW - Tobacco smoking

KW - TSLC1/IGSF4 gene

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