ArticleCellular oncology (Dordrecht, Netherlands)2024
DNA hypomethylation patterns and their impact on the tumor microenvironment in colorectal cancer.
Article in Cellular oncology (Dordrecht, Netherlands), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- SUMOylation-Dependent Repression of BIRC7 by DNMT3a Suppresses Papillary Thyroid Carcinoma Progression.Cell biochemistry and function · 2026Article
- Hypoxia Associated Integration of Epigenetic, Metabolic, and Immune Biomarkers in Blood and Urine for Early Colorectal Cancer Detection: A Multimarker Panel.Diagnostics (Basel, Switzerland) · 2026Article
- Prognostic model construction and drug prediction in colorectal cancer using mitochondrial programmed cell death-related genes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- PSMC4 promotes low-grade glioma progression and predicts poor prognosis.European journal of medical research · 2026Article
- Colorectal Cancer Biomarker Identification via Joint DNA-Methylation and Transcriptomics Analysis Workflow.Genes · 2025Article
- Multi-omics pan-cancer analysis of monocyte to macrophage differentiation-associated (MMD) and its significance in hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2025Article
- Emerging artificial intelligence-driven precision therapies in tumor drug resistance: recent advances, opportunities, and challenges.Molecular cancer · 2025Review
- Identification and validation of crotonylation-related diagnostic markers for lung adenocarcinoma via weighted correlation network analysis and machine learning.Translational lung cancer research · 2025Article
- Single-cell technology reveals the crosstalk between tumor cells and immune cells: driving immune signal transduction and inflammation-mediated cardiac dysfunction in the tumor microenvironment of colorectal cancer.Frontiers in immunology · 2025Article
- TMED9: a potential therapeutic target and prognostic marker in glioma and its implications across pan-cancer contexts.Frontiers in immunology · 2025Article
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Authors and funding
12 authors at 10 institutions in 2 countries.
Funding
Abstract
backgroundRecent research underscores the pivotal role of immune checkpoints as biomarkers in colorectal cancer (CRC) therapy, highlighting the dynamics of resistance and response to immune checkpoint inhibitors. The impact of epigenetic alterations in CRC, particularly in relation to immune therapy resistance, is not fully understood.
methodsWe integrated a comprehensive dataset encompassing TCGA-COAD, TCGA-READ, and multiple GEO series (GSE14333, GSE37892, GSE41258), along with key epigenetic datasets (TCGA-COAD, TCGA-READ, GSE77718). Hierarchical clustering, based on Euclidean distance and Ward's method, was applied to 330 primary tumor samples to identify distinct clusters. The immune microenvironment was assessed using MCPcounter. Machine learning algorithms were employed to predict DNA methylation patterns and their functional enrichment, in addition to transcriptome expression analysis. Genomic mutation profiles and treatment response assessments were also conducted.
resultsOur analysis delineated a specific tumor cluster with CpG Island (CGI) methylation, termed the Demethylated Phenotype (DMP). DMP was associated with metabolic pathways such as oxidative phosphorylation, implicating increased ATP production efficiency in mitochondria, which contributes to tumor aggressiveness. Furthermore, DMP showed activation of the Myc target pathway, known for tumor immune suppression, and exhibited downregulation in key immune-related pathways, suggesting a tumor microenvironment characterized by diminished immunity and increased fibroblast infiltration. Six potential therapeutic agents-lapatinib, RDEA119, WH.4.023, MG.132, PD.0325901, and AZ628-were identified as effective for the DMP subtype.
conclusionThis study unveils a novel epigenetic phenotype in CRC linked to resistance against immune checkpoint inhibitors, presenting a significant step toward personalized medicine by suggesting epigenetic classifications as a means to identify ideal candidates for immunotherapy in CRC. Our findings also highlight potential therapeutic agents for the DMP subtype, offering new avenues for tailored CRC treatment strategies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.