Related Experiment Video
Updated: Dec 31, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Genome-wide analysis reveals the association between alternative splicing and DNA methylation across human solid
Xiaohui Sun1, Yiping Tian2, Jianming Wang3
1Department of Epidemiology & Biostatistics, School of Public Health, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Background:
Dysregulation of alternative splicing (AS) is a critical signature of cancer. However, the regulatory mechanisms of cancer-specific AS events, especially the impact of DNA methylation, are poorly understood.
Methods:
By using The Cancer Genome Atlas (TCGA) SpliceSeq and TCGA data for ten solid tumor types, association analysis was performed to characterize the potential link between cancer-specific AS and DNA methylation. Functional and pathway enrichment analyses were performed, and the protein-protein interaction (PPI) network was constructed with the String website. The prognostic analysis was carried out with multivariate Cox regressions models.
Results:
15,818 AS events in 3955 annotated genes were identified across ten solid tumor types. The different DNA methylation patterns between tumor and normal tissues at the corresponding alternative spliced exon boundaries were shown, and 51.3% of CpG sites (CpGs) revealed hypomethylated in tumors. Notably, 607 CpGs were found to be highly correlated with 369 cancer-specific AS events after permutation tests. Among them, the hypomethylated CpGs account for 52.7%, and the number of down-regulated exons was 173. Furthermore, we found 38 AS events in 35 genes could serve as new molecular biomarkers to predict patient survival.
Conclusions:
Our study described the relationship between DNA methylation and AS events across ten human solid tumor types and provided new insights into intragenic DNA methylation and exon usage during the AS process.
Insights
DNA methylation influences cancer-specific alternative splicing (AS) events. This study identified correlations between DNA methylation patterns and AS, revealing potential biomarkers for predicting patient survival in solid tumors.
Area of Science:
- Cancer Biology
- Epigenetics
- Molecular Oncology
Background:
- Alternative splicing (AS) dysregulation is a hallmark of cancer.
- Mechanisms of cancer-specific AS, particularly DNA methylation's role, remain unclear.
Purpose of the Study:
- To investigate the association between cancer-specific AS events and DNA methylation.
- To identify potential molecular biomarkers for cancer prognosis.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) SpliceSeq and TCGA data for ten solid tumor types.
- Performed association analysis, functional enrichment, pathway analysis, and constructed a protein-protein interaction network.
- Conducted prognostic analysis using multivariate Cox regression models.
Main Results:
- Identified 15,818 AS events in 3955 genes across ten solid tumors.
- Observed distinct DNA methylation patterns, with 51.3% of CpG sites hypomethylated in tumors.
- Found 607 CpGs correlated with 369 cancer-specific AS events, with 52.7% being hypomethylated.
- Discovered 38 AS events in 35 genes as potential prognostic biomarkers.
Conclusions:
- Established a link between DNA methylation and AS events in human solid tumors.
- Provided novel insights into intragenic DNA methylation and exon usage in AS.
- Highlighted potential for AS events as novel biomarkers for cancer patient survival.
Related Concept Videos
01:37Epigenetic Regulation
X-chromosome...
01:46Epigenetic Regulation
02:18Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...