Related Experiment Video
Updated: Dec 30, 2025
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Identification of key genes by integrating DNA methylation and next-generation transcriptome sequencing for
Yang Chen1,2, Lian-Di Liao1,3, Zhi-Yong Wu4
1The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China.
Abstract:
Aberrant DNA methylation leads to abnormal gene expression, making it a significant regulator in the progression of cancer and leading to the requirement for integration of gene expression with DNA methylation. Here, we identified 120 genes demonstrating an inverse correlation between DNA methylation and mRNA expression in esophageal squamous cell carcinoma (ESCC). Sixteen key genes, such as SIX4, CRABP2, and EHD3, were obtained by filtering 10 datasets and verified in paired ESCC samples by qRT-PCR. 5-Aza-dC as a DNA methyltransferase (DNMT) inhibitor could recover their expression and inhibit clonal growth of cancer cells in seven ESCC cell lines. Furthermore, 11 of the 16 genes were correlated with OS (overall survival) and DFS (disease-free survival) in 125 ESCC patients. ChIP-Seq data and WGBS data showed that DNA methylation and H3K27ac histone modification of these key genes displayed inverse trends, suggesting that there was collaboration between DNA methylation and histone modification in ESCC. Our findings illustrate that the integrated multi-omics data (transcriptome and epigenomics) can accurately obtain potential prognostic biomarkers, which may provide important insight for the effective treatment of cancers.
Insights
Aberrant DNA methylation and gene expression are key in esophageal cancer. Researchers found 16 genes with inverse correlations, showing potential as prognostic biomarkers for effective cancer treatment.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Aberrant DNA methylation is a significant driver of cancer progression by altering gene expression.
- Integrating DNA methylation and gene expression data is crucial for understanding cancer.
- Esophageal squamous cell carcinoma (ESCC) requires further investigation into its molecular underpinnings.
Purpose of the Study:
- To identify genes with inverse correlations between DNA methylation and mRNA expression in ESCC.
- To validate these genes as potential prognostic biomarkers.
- To explore the interplay between DNA methylation and histone modifications in ESCC.
Main Methods:
- Bioinformatic analysis of 10 datasets to identify 120 inversely correlated genes.
- Quantitative reverse transcription PCR (qRT-PCR) validation in paired ESCC samples.
- Treatment of ESCC cell lines with a DNA methyltransferase (DNMT) inhibitor (5-Aza-dC).
- Correlation analysis of gene expression with overall survival (OS) and disease-free survival (DFS) in ESCC patients.
- Analysis of ChIP-Seq and Whole Genome Bisulfite Sequencing (WGBS) data.
Main Results:
- Identified 16 key genes (e.g., SIX4, CRABP2, EHD3) showing inverse DNA methylation and mRNA expression correlation in ESCC.
- 5-Aza-dC treatment restored expression of these genes and inhibited ESCC cell growth.
- 11 of the 16 genes were significantly correlated with OS and DFS in 125 ESCC patients.
- Inverse trends observed between DNA methylation and H3K27ac histone modification for these genes, suggesting collaborative regulation.
Conclusions:
- Integrated multi-omics data (transcriptome and epigenomics) effectively identifies prognostic biomarkers in ESCC.
- The identified genes represent potential therapeutic targets and prognostic indicators for esophageal squamous cell carcinoma.
- Understanding the interplay of DNA methylation and histone modification offers insights into ESCC pathogenesis and treatment.
