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

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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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Keywords

  • Immunostaining
  • Lung cancer
  • Methylation
  • SPARC

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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