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Updated: Aug 17, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Genomic screens for genes upregulated by demethylation in colorectal cancer: possible usefulness for clinical
Kazuhiko Ogawa1, Tohru Utsunomiya, Koshi Mimori
1Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Abstract:
Inactivation of tumor suppressor genes may result in clinically aggressive tumors and poor prognoses for cancer patients. This study was conducted to investigate the clinical significance of genomic screens for genes upregulated by demethylation in colorectal cancer. We performed a comprehensive survey of commonly inactivated genes in colorectal cancer through the functional reactivation of epigenetically silenced genes by 5-Azacytidine, using cDNA microarrays containing 12,814 genes. We then investigated the clinical significance of the identified gene in colorectal cancer patients. Among 41 candidate genes identified by this microarray analysis, 31 (76%) harbored CpG islands, and many of the genes were associated with cancer-testis antigens, Wnt inhibitors, growth factors, and cell cycle regulators. Subsequent analysis by quantitative RT-PCR confirmed the reliability of our microarray strategy. In order to elucidate the potential clinical significance of these identified genes, we selected one of these genes, apolipoprotein D (apo D), and investigated its mRNA expression in 63 colorectal cancer patients using quantitative real-time RT-PCR. The mean expression level of Apo D mRNA was significantly lower in cancerous tissues than in non-cancerous tissues (p < 0.01), and a lower expression of Apo D was significantly correlated with lymph node metastasis (p < 0.05), advanced stages (p < 0.05) and poorer overall survival (p < 0.05). These results indicated that a genomic screen for genes upregulated by demethylation may be a useful approach for the identification of genes that are of clinical significance in colorectal cancer patients.
Insights
Genomic screens identifying genes reactivated by demethylation can reveal clinically significant markers in colorectal cancer. Lower apolipoprotein D (apo D) expression correlates with advanced disease and poorer survival.
Area of Science:
- Genomics
- Cancer Biology
- Epigenetics
Background:
- Inactivation of tumor suppressor genes is linked to aggressive tumors and poor cancer prognoses.
- Epigenetic silencing, particularly via DNA methylation, is a common mechanism for gene inactivation in cancer.
Purpose of the Study:
- To investigate the clinical significance of genes upregulated by demethylation in colorectal cancer.
- To identify novel biomarkers for colorectal cancer prognosis using a genomic screening approach.
Main Methods:
- Utilized 5-Azacytidine to reactivate epigenetically silenced genes in colorectal cancer.
- Performed cDNA microarray analysis of 12,814 genes to identify candidate genes.
- Validated gene expression and clinical significance using quantitative real-time RT-PCR in 63 colorectal cancer patients.
Main Results:
- Identified 41 candidate genes upregulated by demethylation, with 76% harboring CpG islands.
- Apolipoprotein D (apo D) mRNA expression was significantly lower in cancerous tissues than non-cancerous tissues (p < 0.01).
- Lower apo D expression correlated with lymph node metastasis (p < 0.05), advanced stages (p < 0.05), and poorer overall survival (p < 0.05).
Conclusions:
- Genomic screening for demethylation-upregulated genes is a viable strategy for identifying clinically significant genes in colorectal cancer.
- Apolipoprotein D may serve as a potential prognostic biomarker for colorectal cancer patients.
