{
  "abstract": "Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, yet molecular features that distinguish indolent tumors from those with progression-associated clinicopathological features remain limited. Here, we integrated single-cell RNA sequencing of 17 PTC samples with copy-number inference and identified a CRABP1-positive malignant epithelial cell population that retained epithelial features (CDH1, KRT19) and exhibited a distinct transcriptional program. In TCGA-THCA bulk data, lower CRABP1 expression was associated with lymph-node metastasis and pathological T-category variation. Functional experiments in complementary thyroid carcinoma cell-line models showed that CRABP1 knockdown increased migration and invasion and was accompanied by an EMT-related transcriptional shift, whereas CRABP1 overexpression showed the opposite pattern. Public methylation analyses showed higher aggregate promoter-region methylation in tumors, whereas methylation of cg02276974, an intron-2/gene-body CpG, was weakly inversely associated with CRABP1 expression (r = -0.2069, R2 = 0.0428; P < 0.001). Decitabine altered migration, invasion, Vimentin-associated, and xenograft phenotypes in CRABP1-manipulated models. Collectively, these results identify a CRABP1-positive malignant epithelial cell state associated with clinicopathological features in PTC and support an invasion-associated suppressive role for CRABP1 in thyroid carcinoma models. The methylation and decitabine findings define a methylation-associated pharmacological context; they do not establish CRABP1-specific or locus-specific epigenetic causality.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Thyroid Surgery, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, Guangdong, China.",
    "Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, China.",
    "The Fourth General Surgery Department of the Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.",
    "Liaoning Fangda General Hospital, Shenyang, Liaoning, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tiancheng Fu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yudong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Guoxiang Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiarong Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Guangfeng Luo"
    },
    {
      "affs": [
        1
      ],
      "name": "Chengcheng Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yanze Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Ziyang Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinghua Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhen Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2rc0e1x63mvca.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1974822",
  "fulltext_url": "https://europepmc.org/articles/PMC13713623",
  "id": "2rc0e1x63mvca",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42952974",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2712|Thyroid Cancer Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7221764902",
  "pdf_url": "https://europepmc.org/articles/PMC13713623?pdf=render",
  "pmcid": "PMC13713623",
  "pmid": "42952974",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2rc0e1x63mvca.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42952974",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952974"
    },
    {
      "first_seen": "2026-10-31T12:24:08Z",
      "native_id": "PMC13713623",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1974822"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2712|Thyroid Cancer Diagnosis and Treatment",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Methylation-associated downregulation of CRABP1 marks an aggressive malignant epithelial cell state in thyroid carcinoma.",
  "title_text": "Methylation-associated downregulation of CRABP1 marks an aggressive malignant epithelial cell state in thyroid carcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:16Z",
  "url": "https://research.draconitic.com/paper/2rc0e1x63mvca",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}