Aberrant methylation of SPARC in human lung cancers

M. Suzuki, C. Hao, T. Takahashi, H. Shigematsu, N. Shivapurkar, U. G. Sathyanarayana, T. Iizasa, T. Fujisawa, K. Hiroshima, A. F. Gazdar

Research output: Contribution to journalArticle

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Abstract

SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca2+-binding matricellular glycoprotein associated with the regulation of cell adhesion and growth. We investigated loss of expression of SPARC gene and promoter methylation in lung cancers and correlated the data with clinicopathological features. We observed loss of SPARC expression in 12 of 20 (60%) lung cancer cell lines. Treatment of expression-negative cell lines with a demethylating agent restored expression in all cases. Methylation frequencies of SPARC gene were 55% in 20 lung cancer cell lines. Primary tumours had methylation at a rate of 69% (119 of 173), while nonmalignant lung tissues (n = 60) had very low rates (3%). In lung adenocarcinomas, SPARC methylation correlated with a negative prognosis (P = 0.0021; relative risk 4.65, 95% confidence interval 1.75-12.35, multivariate Cox's proportional-hazard model). Immunostaining revealed protein expression in bronchial epithelium (weak intensity) and in juxtatumoral stromal tissues (strong intensity) accompanied by frequent loss in cancer cells that correlated with the presence of methylation (P < 0.001). Our findings are of biological interest and potentially of clinical importance in human lung cancers.

Original languageEnglish (US)
Pages (from-to)942-948
Number of pages7
JournalBritish Journal of Cancer
Volume92
Issue number5
DOIs
StatePublished - Mar 14 2005

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Methylation
Lung Neoplasms
Cysteine
Proteins
Cell Line
Proportional Hazards Models
Cell Adhesion
Genes
human SPARC protein
Neoplasms
Glycoproteins
Epithelium
Confidence Intervals
Lung
Growth

Keywords

  • Immunostaining
  • Lung cancer
  • Methylation
  • SPARC

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Suzuki, M., Hao, C., Takahashi, T., Shigematsu, H., Shivapurkar, N., Sathyanarayana, U. G., ... Gazdar, A. F. (2005). Aberrant methylation of SPARC in human lung cancers. British Journal of Cancer, 92(5), 942-948. https://doi.org/10.1038/sj.bjc.6602376

Aberrant methylation of SPARC in human lung cancers. / Suzuki, M.; Hao, C.; Takahashi, T.; Shigematsu, H.; Shivapurkar, N.; Sathyanarayana, U. G.; Iizasa, T.; Fujisawa, T.; Hiroshima, K.; Gazdar, A. F.

In: British Journal of Cancer, Vol. 92, No. 5, 14.03.2005, p. 942-948.

Research output: Contribution to journalArticle

Suzuki, M, Hao, C, Takahashi, T, Shigematsu, H, Shivapurkar, N, Sathyanarayana, UG, Iizasa, T, Fujisawa, T, Hiroshima, K & Gazdar, AF 2005, 'Aberrant methylation of SPARC in human lung cancers', British Journal of Cancer, vol. 92, no. 5, pp. 942-948. https://doi.org/10.1038/sj.bjc.6602376
Suzuki M, Hao C, Takahashi T, Shigematsu H, Shivapurkar N, Sathyanarayana UG et al. Aberrant methylation of SPARC in human lung cancers. British Journal of Cancer. 2005 Mar 14;92(5):942-948. https://doi.org/10.1038/sj.bjc.6602376
Suzuki, M. ; Hao, C. ; Takahashi, T. ; Shigematsu, H. ; Shivapurkar, N. ; Sathyanarayana, U. G. ; Iizasa, T. ; Fujisawa, T. ; Hiroshima, K. ; Gazdar, A. F. / Aberrant methylation of SPARC in human lung cancers. In: British Journal of Cancer. 2005 ; Vol. 92, No. 5. pp. 942-948.
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