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Peer-reviewedCC BY-NC-NDJournal of gastrointestinal oncology

ANGPT2 promotes angiogenesis and immunosuppressive microenvironment in colorectal cancer.

  • Chunhui Chen1
  • Sufen Wei1
  • Zhiqiang Peng2
  • Shaohua Li2
  • Lu Han1
  • Wei Fang3
  • Yi Cheng1
  • Jianfeng Zheng2
  • Aling Wang4
4 affiliations
  1. 1The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  2. 2State Key Laboratory of Medical Proteomics, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
  3. 3Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
  4. 4Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine, Zhongshan, China.
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Abstract

The Angiopoietin-Tie2 system is crucial in tumor angiogenesis for colorectal cancer (CRC), while investigations into integrating angiopoietin-Tie2 into the booming immunotherapy are underway. Here, we investigated the expression patterns and prognostic value of the Angiopoietin-Tie2 system in CRC. The expression patterns of angiopoietin-2 (ANGPT2) and angiopoietin-1 (ANGPT1), two major ligands of the angiopoietin-Tie2 system, as well as their correlation with clinical characteristics and prognosis were analyzed in The Cancer Genome Atlas (TCGA), and the related functions based on protein-protein interaction (PPI) networks in CRC were explored. The impact of ANGPT2 on tumor angiogenesis and immunity was validated in vitro and in vivo. ANGPT2 expression is upregulated in CRC, while ANGPT1 shows an opposite trend, but neither affects clinical characteristics. Kaplan-Meier survival curves and multivariate Cox analysis suggest that only high expression of ANGPT2 is associated with a poor prognosis in CRC. ANGPT2 and ANGPT1 are mainly involved in regulation of vasculature and cell chemotaxis migration. Knockdown of ANGPT2 reduced angiogenesis in vitro, and suppressed the immunosuppressive microenvironment involving CXCL12, including recruitment and differentiation of monocytes, M2 polarization of macrophages and exclusion of effector T cells, ultimately suppressed tumor growth in vivo. ANGPT2, rather than ANGPT1, likely plays a significant role in vascular regulation and immune landscape in CRC.

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Cite

BibTeXRIS
BibTeX
@article{chen2026angpt2,
  title = {{ANGPT2 promotes angiogenesis and immunosuppressive microenvironment in colorectal cancer.}},
  author = {Chunhui Chen and Sufen Wei and Zhiqiang Peng and Shaohua Li and Lu Han and Wei Fang and Yi Cheng and Jianfeng Zheng and Aling Wang},
  journal = {Journal of gastrointestinal oncology},
  year = {2026},
  month = aug,
  doi = {10.21037/jgo-2025-1-965},
  url = {https://europepmc.org/article/MED/42996853},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - ANGPT2 promotes angiogenesis and immunosuppressive microenvironment in colorectal cancer.
AU  - Chunhui Chen
AU  - Sufen Wei
AU  - Zhiqiang Peng
AU  - Shaohua Li
AU  - Lu Han
AU  - Wei Fang
AU  - Yi Cheng
AU  - Jianfeng Zheng
AU  - Aling Wang
PY  - 2026
DA  - 2026/08/17
JO  - Journal of gastrointestinal oncology
DO  - 10.21037/jgo-2025-1-965
UR  - https://europepmc.org/article/MED/42996853
AB  - The Angiopoietin-Tie2 system is crucial in tumor angiogenesis for colorectal cancer (CRC), while investigations into integrating angiopoietin-Tie2 into the booming immunotherapy are underway. Here, we investigated the expression patterns and prognostic value of the Angiopoietin-Tie2 system in CRC. The expression patterns of angiopoietin-2 (ANGPT2) and angiopoietin-1 (ANGPT1), two major ligands of the angiopoietin-Tie2 system, as well as their correlation with clinical characteristics and prognosis were analyzed in The Cancer Genome Atlas (TCGA), and the related functions based on protein-protein interaction (PPI) networks in CRC were explored. The impact of ANGPT2 on tumor angiogenesis and immunity was validated in vitro and in vivo. ANGPT2 expression is upregulated in CRC, while ANGPT1 shows an opposite trend, but neither affects clinical characteristics. Kaplan-Meier survival curves and multivariate Cox analysis suggest that only high expression of ANGPT2 is associated with a poor prognosis in CRC. ANGPT2 and ANGPT1 are mainly involved in regulation of vasculature and cell chemotaxis migration. Knockdown of ANGPT2 reduced angiogenesis in vitro, and suppressed the immunosuppressive microenvironment involving CXCL12, including recruitment and differentiation of monocytes, M2 polarization of macrophages and exclusion of effector T cells, ultimately suppressed tumor growth in vivo. ANGPT2, rather than ANGPT1, likely plays a significant role in vascular regulation and immune landscape in CRC.
SN  - 2078-6891
SN  - 2219-679X
ER  -