SOSTDC1 down-regulation of expression involves CpG methylation and is a potential prognostic marker in gastric cancer

Gopisetty Gopal1, Uthandaraman Mahalinga Raja, Sundersingh Shirley

  • 1Department of Molecular Oncology, Cancer Institute (Women's India Association), Chennai, India.

Cancer Genetics
|July 9, 2013
PubMed

Insights

Sclerostin domain containing 1 (SOSTDC1) is epigenetically silenced by methylation in gastric cancer, leading to reduced expression. SOSTDC1 acts as a tumor suppressor, and its expression predicts better patient survival.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Sclerostin domain containing 1 (SOSTDC1) expression is decreased in several cancers.
  • Gastric cancer exhibits complex molecular alterations contributing to its progression.

Purpose of the Study:

  • To investigate the role of epigenetic mechanisms in SOSTDC1 down-regulation in gastric cancer.
  • To evaluate SOSTDC1 as a potential prognostic biomarker and tumor suppressor in gastric cancer.

Main Methods:

  • Analysis of SOSTDC1 mRNA and protein expression in gastric cancer cell lines and tissues.
  • Reporter assays and gene reactivation studies using DNA demethylating and HDAC inhibitory agents.
  • Methylation-specific PCR to assess SOSTDC1 promoter CpG methylation.
  • Correlation analysis between SOSTDC1 expression, methylation status, clinicopathological features, and patient survival.

Main Results:

  • SOSTDC1 mRNA was down-regulated in gastric cancer cell lines.
  • Epigenetic modifications, including promoter methylation and HDAC inhibition, influenced SOSTDC1 expression.
  • A significant correlation was observed between SOSTDC1 promoter methylation and reduced mRNA expression in tumors.
  • Down-regulated SOSTDC1 protein expression was found in a majority of gastric tumors compared to normal tissues.
  • SOSTDC1 expression was associated with improved overall and disease-free survival.
  • Overexpression of SOSTDC1 suppressed cell proliferation, cell cycle progression, and anchorage-independent growth in gastric cancer cells.

Conclusions:

  • Epigenetic silencing via promoter methylation contributes to SOSTDC1 down-regulation in gastric cancer.
  • SOSTDC1 functions as a tumor suppressor in gastric cancer.
  • SOSTDC1 expression serves as a potential prognostic factor for gastric cancer patients.

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