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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
07:50

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

Aberrant methylation of SPARC in human lung cancers

M Suzuki1, C Hao, T Takahashi

  • 1Hamon Center for Therapeutic Oncology Research, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. smakoto@chiba-cc.jp

British Journal of Cancer
|March 10, 2005
PubMed

Insights

Secreted protein acidic and rich in cysteine (SPARC) loss is frequent in lung cancer due to gene promoter methylation. Restoring SPARC expression is possible, and its methylation indicates a poorer prognosis in lung adenocarcinomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matricellular glycoprotein regulating cell adhesion and growth.
  • SPARC's role in lung cancer pathogenesis and its epigenetic regulation remain incompletely understood.

Purpose of the Study:

  • To investigate the frequency of SPARC gene expression loss and promoter methylation in lung cancers.
  • To correlate SPARC alterations with clinicopathological features and patient prognosis.

Main Methods:

  • Analysis of SPARC expression in lung cancer cell lines and primary tumors.
  • Assessment of SPARC promoter methylation using demethylating agents and direct methylation analysis.
  • Immunohistochemical staining for SPARC protein expression.
  • Correlation analysis with clinicopathological data and survival outcomes using Cox's proportional-hazard model.

Main Results:

  • Loss of SPARC expression was observed in 60% of lung cancer cell lines, with restoration upon demethylation.
  • SPARC promoter methylation was frequent in lung cancer cell lines (55%) and primary tumors (69%), contrasting with nonmalignant lung tissues (3%).
  • SPARC methylation significantly correlated with a negative prognosis in lung adenocarcinomas (P=0.0021) and loss of protein expression in cancer cells (P<0.001).

Conclusions:

  • Epigenetic silencing of SPARC via promoter methylation is a common event in lung cancer.
  • SPARC methylation is a potential biomarker for poor prognosis in lung adenocarcinoma.
  • Restoration of SPARC expression by demethylating agents suggests therapeutic potential.

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