ArticleWorld journal of hepatology2025
Chromatin accessibility module identified by single-cell sequencing underlies the diagnosis and prognosis of hepatocellular carcinoma.
Article in World journal of hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHepatocellular carcinoma (HCC) is notorious for its aggressive progression and dismal prognosis, with chromatin accessibility dynamics emerging as pivotal yet poorly understood drivers.
aimTo dissect how multilayered chromatin regulation sustains oncogenic transcription and tumor-stroma crosstalk in HCC, we combined multiomics single cell analysis.
methodsWe integrated single-cell RNA sequencing and paired single-cell assay for transposase-accessible chromatin with sequencing data of HCC samples, complemented by bulk RNA sequencing validation across The Cancer Genome Atlas, Liver Cancer Institute, and GSE25907 cohorts. Cell type-specific chromatin architectures were resolved
resultsMalignant hepatocytes exhibited expanded chromatin accessibility profiles, characterized by increased numbers of accessible peaks and larger physical regions despite reduced peak intensity. Enhancer-like peaks enriched in malignant regulation, forming long-range hubs. Eighteen enhancer-like peak-related genes showed tumor-specific overexpression and diagnostic accuracy, correlating with poor prognosis. Intercellular coaccessibility analysis revealed tumor-stroma symbiosis
conclusionMultilayered chromatin reprogramming sustains HCC progression through tumor-stroma crosstalk and
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