{
  "abstract": "Partially methylated domains (PMDs) represent extensive genome-wide hypomethylated regions that drive genomic instability and proto-oncogene activation. However, their complex regulatory influence on tumor-specific transcriptional networks remains largely elusive. In this study, we developed a robust computational pipeline to characterize aberrant PMD landscapes across pan-cancer. We specifically focused on the epigenetic features associated with transcriptional dysregulation in esophageal squamous cell carcinoma (ESCC). By analyzing gene expression patterns, we classified PMDs into four distinct classes and revealed that several immunosuppressive genes were recurrently activated within Tumor-PMDs across various cancers. While these PMDs were generally marked by elevated repressive H3K27me3 and diminished active histone modifications, the activated genes within them paradoxically exhibited a precise, localized enrichment of H3K9ac and H3K27ac near their transcription start sites (TSSs). This localized epigenetic rewiring suggests a potential correlation where collaborative histone modification landscapes may shape oncogenic chromatin remodeling to license transcriptional dysregulation. Furthermore, we identified a robust co-expression axis between the prognostic gene ATP6V0D2 and established immune checkpoints (HAVCR2, TDO2). Elevated ATP6V0D2 expression was found to potentially contribute to ESCC progression and poor prognosis by activating the complement system and epithelial-mesenchymal transition (EMT) pathways. Capitalizing on these findings, virtual screening and in vitro validation suggested that caffeic acid could act as a potential ATP6V0D2-binding compound, effectively suppressing the migration and viability of ESCC cells. This study further nominates caffeic acid as a candidate compound for further mechanistic and therapeutic investigation in ESCC.",
  "abstract_shown": true,
  "affiliations": [
    "Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
    "Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.",
    "Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, Jiangsu, China.",
    "Jiangsu Key Laboratory of Coal-Based Greenhouse Gas Control and Utilization, China University of Mining and Technology, Xuzhou, Jiangsu, China.",
    "Carbon Neutrality Institute, China University of Mining and Technology, Xuzhou, Jiangsu, China.",
    "Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yan Huang",
      "orcid": "0000-0003-2039-7167"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jing Xue"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xue Luan"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Huixia Zhang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jingke Ding"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jintao Xu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zhongjun Zhao"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Quanda Li"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Kunkun Tu"
    },
    {
      "affs": [
        5
      ],
      "name": "Xinyu Wang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Wenjie Ge",
      "orcid": "0000-0002-6034-648X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9p52swcn5df2t.bib",
  "cited_by": 0,
  "doi": "10.1080/15592294.2026.2745292",
  "fulltext_url": "https://europepmc.org/articles/PMC13682402",
  "id": "9p52swcn5df2t",
  "issns": [
    "1559-2294",
    "1559-2308"
  ],
  "landing_url": "https://europepmc.org/article/MED/42891659",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7222814554",
  "pdf_url": "https://europepmc.org/articles/PMC13682402?pdf=render",
  "pmcid": "PMC13682402",
  "pmid": "42891659",
  "published": "2026-10-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9p52swcn5df2t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42891659",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42891659"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Epigenetics and DNA Methylation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Diverse patterns of transcriptional regulation and epigenetic reprogramming within PMDs contribute to ESCC progression by regulating EMT and immunosuppression.",
  "title_text": "Diverse patterns of transcriptional regulation and epigenetic reprogramming within PMDs contribute to ESCC progression by regulating EMT and immunosuppression.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/9p52swcn5df2t",
  "venue": "Epigenetics",
  "versions": []
}