{
  "abstract": "Tumor-adjacent mucosa is commonly used as a normal reference in colorectal cancer (CRC) transcriptomic studies, but its relationship with distant normal mucosa and tumor tissue remains unclear. Here, we performed bulk RNA sequencing of paired distant normal, adjacent, and tumor tissues from 25 patients with CRC and used these three tissue states to construct an ordered normal-adjacent-tumor (N-A-T) expression continuum. Although adjacent mucosa was globally closer to distant normal mucosa and showed no significant differential expression by pairwise analysis, a limma-based linear trend model identified widespread monotonic transcriptional changes along the N-A-T continuum. Tumor-directed genes were enriched in translation, RNA processing, cell-cycle activity, and proliferation-related pathways, whereas genes decreasing along this axis were associated with oxidative metabolism and epithelial homeostasis. A trend gene-based N-A-T score positioned adjacent mucosa between normal and tumor tissues in external bulk cohorts and was associated with proliferative and immune-low molecular states in CRC. Single-cell RNA-seq analysis localized this signal mainly to epithelial cells and associated higher scores with proliferative and stem-like epithelial states. In conclusion, CRC-adjacent mucosa is not fully equivalent to distant normal mucosa but carries coordinated tumor-directed transcriptional changes mainly associated with epithelial-cell programs.",
  "abstract_shown": true,
  "affiliations": [
    "School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.",
    "Institute of Herbgenomics, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.",
    "Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610032, China.",
    "School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.",
    "School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550025, China.",
    "Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610032, China. lizhuohong@cdutcm.edu.cn.",
    "Sichuan Provincial Engineering Technology Research Center of Natural Small Molecule Drug, Tianfu TCM Innovation Harbour, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611930, China. zhengchuan@cdutcm.edu.cn.",
    "TCM Prevention and Treatment of Metabolic and Chronic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, China. zhengchuan@cdutcm.edu.cn.",
    "School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China. songchi@cdutcm.edu.cn.",
    "Institute of Herbgenomics, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China. songchi@cdutcm.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sha Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Long Wu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ruoshi Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Xin Luo"
    },
    {
      "affs": [
        3
      ],
      "name": "Xueni Zhao"
    },
    {
      "affs": [
        4
      ],
      "name": "Liangrui Shi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wei Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lishan Ding"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhaotong Cong"
    },
    {
      "affs": [
        5
      ],
      "name": "Zhuohong Li"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Chuan Zheng"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Chi Song",
      "orcid": "0000-0003-3904-963X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6pgt824xy7eb1.bib",
  "cited_by": 0,
  "doi": "10.1007/s10142-026-02066-w",
  "fulltext_url": "https://europepmc.org/articles/PMC13676565",
  "id": "6pgt824xy7eb1",
  "issns": [
    "1438-793X",
    "1438-7948"
  ],
  "landing_url": "https://europepmc.org/article/MED/42891902",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7165553235",
  "pdf_url": "https://europepmc.org/articles/PMC13676565?pdf=render",
  "pmcid": "PMC13676565",
  "pmid": "42891902",
  "published": "2026-10-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6pgt824xy7eb1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42891902",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42891902"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Integrative transcriptomic analysis reveals tumor-adjacent mucosal remodeling in colorectal cancer.",
  "title_text": "Integrative transcriptomic analysis reveals tumor-adjacent mucosal remodeling in colorectal cancer.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/6pgt824xy7eb1",
  "venue": "Functional & integrative genomics",
  "versions": []
}