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Peer-reviewedCC BY-NC-NDFunctional & integrative genomics

Integrative transcriptomic analysis reveals tumor-adjacent mucosal remodeling in colorectal cancer.

  • Sha Wu1,2
  • Long Wu3
  • Ruoshi Li1,2
  • Xin Luo4
  • Xueni Zhao4
  • Liangrui Shi5
  • Wei Liu1,2
  • Lishan Ding1,2
  • Zhaotong Cong1,2
  • Zhuohong Li6
  • Chuan Zheng7,8
  • Chi Song9,10
10 affiliations
  1. 1School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
  2. 2Institute of Herbgenomics, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
  3. 3Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610032, China.
  4. 4School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
  5. 5School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550025, China.
  6. 6Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610032, China. [email protected].
  7. 7Sichuan Provincial Engineering Technology Research Center of Natural Small Molecule Drug, Tianfu TCM Innovation Harbour, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611930, China. [email protected].
  8. 8TCM 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. [email protected].
  9. 9School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China. [email protected].
  10. 10Institute of Herbgenomics, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China. [email protected].
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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.

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Cite

BibTeXRIS
BibTeX
@article{wu2026integrative,
  title = {{Integrative transcriptomic analysis reveals tumor-adjacent mucosal remodeling in colorectal cancer.}},
  author = {Sha Wu and Long Wu and Ruoshi Li and Xin Luo and Xueni Zhao and Liangrui Shi and Wei Liu and Lishan Ding and Zhaotong Cong and Zhuohong Li and Chuan Zheng and Chi Song},
  journal = {Functional \& integrative genomics},
  year = {2026},
  month = oct,
  doi = {10.1007/s10142-026-02066-w},
  url = {https://europepmc.org/article/MED/42891902},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Integrative transcriptomic analysis reveals tumor-adjacent mucosal remodeling in colorectal cancer.
AU  - Sha Wu
AU  - Long Wu
AU  - Ruoshi Li
AU  - Xin Luo
AU  - Xueni Zhao
AU  - Liangrui Shi
AU  - Wei Liu
AU  - Lishan Ding
AU  - Zhaotong Cong
AU  - Zhuohong Li
AU  - Chuan Zheng
AU  - Chi Song
PY  - 2026
DA  - 2026/10/17
JO  - Functional & integrative genomics
DO  - 10.1007/s10142-026-02066-w
UR  - https://europepmc.org/article/MED/42891902
AB  - 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.
SN  - 1438-793X
SN  - 1438-7948
ER  -