ArticleScientific reports2025
Epigenetic evolution and clinicopathological implications of distinct DNA methylation profiles in pancreatic ductal adenocarcinoma.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Biomarker discovery and patient stratification in pancreatic cancer using incomplete multi-omics data.PLoS computational biology · 2026Article
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10 authors.
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Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with poor prognosis. We investigated intratumoral deoxyribonucleic acid methylation heterogeneity by analyzing 44 tumor samples and 5 normal samples from 6 cases of PDAC by using high-resolution methylation arrays. Two distinct methylation profiles were identified: T1, which is similar to normal pancreatic tissue and is associated with well-differentiated histology, and T2, which is significantly different from normal tissue and is linked to poorly differentiated morphology and squamous features. Validation using The Cancer Genome Atlas (TCGA) confirmed these profiles and revealed the association of T2 with shorter disease-free survival (p = 0.04). Differentially methylated region analysis identified the substantial hypomethylation of transcription regulation genes in T2 profiles (false discovery rate [FDR] q < 0.001). Gene set enrichment analysis with TCGA gene expression data demonstrated the upregulation of DNA repair and MYC target genes in T2 samples (FDR q < 0.001). Phylogenetic analysis with our multi-sampling dataset suggested an evolutionary trajectory from T1 to T2 profiles coinciding with aggressive phenotypes and increased genomic instability. Cases exhibited varying degrees of intratumoral heterogeneity from distinctly separated clusters to minimal differences. This comprehensive characterization of the epigenetic landscape of PDAC provides insights into tumor evolution and heterogeneity with potential implications for patient stratification and the development of epigenetic-based diagnostic and therapeutic strategies.
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