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Updated: Dec 31, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Clinical significance of chromatin remodeling factor CHD5 expression in gastric cancer
Tadayoshi Hashimoto1, Yukinori Kurokawa1, Noriko Wada1
1Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Abstract:
Chromodomain helicase DNA-binding 5 (CHD5), which is a member of the CHD family, has been identified as a tumor suppressor gene in a variety of malignancies. The aim of the current study was to clarify the clinical significance of CHD5 expression in gastric cancer. CHD5 expression was evaluated using immunohistochemistry (IHC) in 154 specimens resected from patients with gastric cancer from January 2011 to December 2013, and assessed its relationships with clinicopathological characteristics and survival. In vitro cell proliferation, invasion, and migration assays and western blotting analysis were performed to clarify the role of CHD5 in human gastric cancer cell lines. Of a total of 154 patients, 57 (37.0%) exhibited low CHD5 expression, which was significantly associated with positive lymphatic invasion (P=0.032), advanced pT status (P=0.011), and advanced pStage (P=0.014). Overall survival (OS) in patients with low CHD5 expression was significantly worse compared with patients with high CHD5 expression (hazard ratio, 1.96; 95% confidence interval, 1.09-3.45; log-rank P=0.023). Cox multivariate analysis for OS revealed that CHD5 expression was an independent prognostic factor with age and pN status. In vitro, the upregulation of CHD5 in gastric cancer cells with low CHD5 expression significantly decreased cell proliferation, migration and invasion. CHD5 was associated with the regulation of multiple cancer-related targets, including p53 and enhancer of zeste homolog 2 (EZH2) in western blotting analysis. In conclusion, since CHD5 regulated multiple cancer-related targets, its expression may be a useful prognostic biomarker in patients with gastric cancer.
Insights
Chromodomain helicase DNA-binding 5 (CHD5) acts as a tumor suppressor in gastric cancer. Low CHD5 expression correlates with poorer survival and advanced disease, suggesting its potential as a prognostic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromodomain helicase DNA-binding 5 (CHD5) is a member of the CHD family and a known tumor suppressor gene.
- Its clinical significance in gastric cancer, however, requires further elucidation.
Purpose of the Study:
- To investigate the clinical significance of CHD5 expression in gastric cancer.
- To assess the relationship between CHD5 expression and clinicopathological characteristics, patient survival, and its functional role in gastric cancer cell lines.
Main Methods:
- Immunohistochemistry (IHC) was used to evaluate CHD5 expression in 154 gastric cancer specimens.
- In vitro assays (cell proliferation, invasion, migration) and western blotting were performed.
- Statistical analyses, including Cox multivariate analysis, were conducted to determine prognostic value.
Main Results:
- Low CHD5 expression was observed in 37.0% of patients and was significantly associated with positive lymphatic invasion, advanced pT status, and advanced pStage.
- Patients with low CHD5 expression had significantly worse overall survival (OS).
- CHD5 expression was identified as an independent prognostic factor for OS, alongside age and pN status. In vitro studies showed CHD5 upregulation suppressed cell proliferation, migration, and invasion.
Conclusions:
- CHD5 expression is significantly associated with clinicopathological features and survival in gastric cancer patients.
- CHD5 acts as a tumor suppressor by inhibiting cell proliferation, invasion, and migration.
- CHD5 may serve as a valuable prognostic biomarker for gastric cancer.
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