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Updated: May 10, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
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.
Abstract:
Sclerostin domain containing 1 (SOSTDC1) is reportedly down-regulated in various cancers. Our purpose was to study whether epigenetic mechanisms were involved in the down-regulation of expression in gastric cancer. Expression analysis of SOSTDC1 in gastric cancer cell lines indicated mRNA down-regulation. Our reporter assays and gene reactivation studies using 5-aza-2'-deoxycytidine, a DNA demethylating agent, and trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, demonstrated that epigenetic mechanisms are involved in the down-regulation of SOSTC1 expression. Methylation analysis of the SOSTDC1 promoter CpGs using methylation-specific polymerase chain reaction analysis revealed methylation in gastric cancer cell lines and tissue samples. A majority of tumors (17 of 18) with observed methylation exhibited down-regulation of mRNA expression relative to apparently normal gastric tissues. Immunoreactivity for SOSTDC1 in gastric tumors (24 of 46, 52.1%) was down-regulated relative to normal tissues (36 of 38, 94.7%) (P = 0.00001). The difference in expression between gastric tumor subtypes, intestinal and diffuse, was significant (P = 0.040). Expression of SOSTDC1 in gastric tumors increased the probability of both overall and disease-free survival. When overexpressed in AGS cells, cell proliferation, cell cycle progression, and anchorage-independent growth was repressed. The present findings indicate SOSTDC1 down-regulation involves methylation; SOSTDC1 expression is a potential prognostic factor and tumor suppressor in gastric cancer.
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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