ArticleProceedings of the National Academy of Sciences of the United States of America2023
Transcription factor expression repertoire basis for epigenetic and transcriptional subtypes of colorectal cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Pituitary Neuroendocrine Tumor or Pituitary Adenoma? Let's Ask the Epigenome!Endocrine pathology · 2025Pooled it
- Colorectal Adenocarcinoma: A Comprehensive Narrative Review of Molecular Pathogenesis, Metabolic Vulnerabilities, and Therapeutic Potential of Sorghum Polyphenols.Analytical cellular pathology (Amsterdam) · 2026Review
- Unravelling the genetics and epigenetics of the ageing tumour microenvironment in cancer.Nature reviews. Cancer · 2025Review
- Multiomics Signature Reveals Network Regulatory Mechanisms in a CRC Continuum.International journal of molecular sciences · 2025Article
- Early colorectal cancer diagnosis: A novel methylated stool DNA model enhanced the diagnostic efficiency.United European gastroenterology journal · 2025Article
- The Role of DNA Methylation in Gastrointestinal Disease: An Expanded Review of Malignant and Nonmalignant Gastrointestinal Diseases.Gastroenterology · 2025Review
- ETV4-Mediated PD-L1 Upregulation Promotes Immune Evasion and Predicts Poor Immunotherapy Response in Melanoma.Oncology research · 2025Article
- Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2.Acta biochimica et biophysica Sinica · 2024Article
- Transcription factor expression repertoire basis for epigenetic and transcriptional subtypes of colorectal cancers.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Colorectal cancers (CRCs) form a heterogenous group classified into epigenetic and transcriptional subtypes. The basis for the epigenetic subtypes, exemplified by varying degrees of promoter DNA hypermethylation, and its relation to the transcriptional subtypes is not well understood. We link cancer-specific transcription factor (TF) expression alterations to methylation alterations near TF-binding sites at promoter and enhancer regions in CRCs and their premalignant precursor lesions to provide mechanistic insights into the origins and evolution of the CRC molecular subtypes. A gradient of TF expression changes forms a basis for the subtypes of abnormal DNA methylation, termed CpG-island promoter DNA methylation phenotypes (CIMPs), in CRCs and other cancers. CIMP is tightly correlated with cancer-specific hypermethylation at enhancers, which we term CpG-enhancer methylation phenotype (CEMP). Coordinated promoter and enhancer methylation appears to be driven by downregulation of TFs with common binding sites at the hypermethylated enhancers and promoters. The altered expression of TFs related to hypermethylator subtypes occurs early during CRC development, detectable in premalignant adenomas. TF-based profiling further identifies patients with worse overall survival. Importantly, altered expression of these TFs discriminates the transcriptome-based consensus molecular subtypes (CMS), thus providing a common basis for CIMP and CMS subtypes.
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Registered trials
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