Epigenetic Landscapes and Stromal Epithelial Crosstalk in Colorectal Adenocarcinoma: Histomorphological Signatures of Tumor Progression
Keywords:
colorectal adenocarcinoma, epigenetic regulation, tumor microenvironment, cancer-associated fibroblast, histomorphologyAbstract
To comprehensively review the current understanding of epigenetic regulation and stromal–epithelial crosstalk in colorectal adenocarcinoma and to elucidate their correlation with histomorphological signatures of tumor progression. A systematic narrative review was conducted using PubMed, Scopus, and Web of Science databases for articles published between 2021 and 2026. Keywords included colorectal cancer, epigenetic regulation, tumor microenvironment, cancer-associated fibroblast, stromal epithelial interaction, metabolic reprogramming, and histopathology. Only peer-reviewed articles focusing on molecular mechanisms and histological correlations were included. Recent evidence demonstrates that DNA methylation, histone modification, and non-coding RNA networks orchestrate transcriptional reprogramming in colorectal adenocarcinoma. These epigenetic alterations interact dynamically with cancer-associated fibroblasts, immune cells, extracellular matrix components, and metabolic pathways within the tumor microenvironment. Crosstalk mechanisms mediated by cytokines, growth factors, and extracellular vesicles contribute to epithelial–mesenchymal plasticity, tumor budding, desmoplastic reaction, and vascular remodeling. Spatial transcriptomics further reveals that stromal activation correlates with aggressive histomorphological patterns and unfavorable clinical outcomes. Epigenetic landscapes and stromal–epithelial communication are central determinants of colorectal adenocarcinoma progression. Their integration with histopathological evaluation offers promising opportunities for biomarker development and targeted therapeutic strategies.
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