{
  "abstract": "Background\n\nColorectal cancer (CRC) is characterized by marked epithelial heterogeneity and dynamic tumor-microenvironment interactions. However, epithelial states associated with progression across the normal-adenoma-carcinoma sequence remain incompletely defined.Methods\n\nSingle-cell RNA sequencing data from normal colorectal mucosa, adenoma, and tumor tissues were analyzed using inferCNV, Monocle, Slingshot, CytoTRACE, CellChat, and SCENIC. An OLFM4⁺ tumor cell risk score (OTRS) was constructed using Cox and LASSO regression, and TIMP1 function was evaluated in vitro.Results\n\nEight major cell types and nine tumor epithelial subtypes were identified. C3 OLFM4⁺ cells showed elevated transcriptional activity, stemness, metabolic activity, and greater representation in carcinoma than adenoma tissues. Trajectory analyses positioned these cells in an early-to-intermediate transitional state. CellChat predicted prominent fibroblast-C3 OLFM4⁺ interactions, including a putative WNT2B-FZD/LRP axis, while SCENIC identified XBP1, NFIA, PPARG, HDAC2, and UBE2K as subtype-associated regulators. The C3 OLFM4⁺-derived OTRS stratified prognosis; high OTRS was associated with poorer survival, macrophage-enriched infiltration, higher stromal, immune, and TIDE scores, and differential predicted drug sensitivity. TIMP1 knockdown suppressed malignant behaviors in CRC cells.Conclusion\n\nC3 OLFM4⁺ cells represent a stem-like, metabolically active tumor epithelial state associated with CRC progression, fibroblast-derived WNT signaling, immune-evasion-related features, and unfavorable prognosis. The OTRS model may support prognostic and therapeutic assessment, while TIMP1 contributes to malignant CRC cell behavior.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: lr1999@126.com.",
    "Department of Reproductive Medicine, Hubei University of Medicine, Xiangyang No. 1 People's Hospital, Xiangyang, China.",
    "Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.",
    "Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People's Republic of China.",
    "Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250014, China. Electronic address: sl138630@163.com.",
    "Department of Traditional Chinese Medicine (TCM) Proctology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China. Electronic address: dabing727@126.com.",
    "Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. Electronic address: wenchihlee@sina.com.",
    "Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: linjiang@longhua.net."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rui Leng"
    },
    {
      "affs": [
        1
      ],
      "name": "Xi Cui"
    },
    {
      "affs": [
        2
      ],
      "name": "Xinyu Wu"
    },
    {
      "affs": [
        3
      ],
      "name": "Yang Zhao"
    },
    {
      "affs": [
        4
      ],
      "name": "Lei Sun"
    },
    {
      "affs": [
        5
      ],
      "name": "Haimin Jin"
    },
    {
      "affs": [
        6
      ],
      "name": "Wenzhi Li"
    },
    {
      "affs": [
        7
      ],
      "name": "Jiang Lin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/74p2kppbp686t.bib",
  "cited_by": 0,
  "doi": "10.1016/j.tranon.2026.103066",
  "fulltext_url": "https://europepmc.org/articles/PMC13694951",
  "id": "74p2kppbp686t",
  "issns": [
    "1936-5233"
  ],
  "landing_url": "https://europepmc.org/article/MED/42887063",
  "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|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7222679644",
  "pdf_url": "https://europepmc.org/articles/PMC13694951?pdf=render",
  "pmcid": "PMC13694951",
  "pmid": "42887063",
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/74p2kppbp686t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42887063",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42887063"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Single-cell transcriptomic and immune microenvironment analyses reveal a TIMP1-associated OLFM4⁺ tumor epithelial program linked to colorectal cancer progression and immune evasion.",
  "title_text": "Single-cell transcriptomic and immune microenvironment analyses reveal a TIMP1-associated OLFM4⁺ tumor epithelial program linked to colorectal cancer progression and immune evasion.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/74p2kppbp686t",
  "venue": "Translational oncology",
  "versions": []
}