2. Academic Validation
  3. Identification of the "Collagen-Macrophage" sub-category of patients with colorectal cancer as an extension of the CMS4 subtype with THBS2 as a therapeutic target

Identification of the "Collagen-Macrophage" sub-category of patients with colorectal cancer as an extension of the CMS4 subtype with THBS2 as a therapeutic target

  • BMC Gastroenterol. 2025 May 8;25(1):342. doi: 10.1186/s12876-025-03918-8.
Shuwen Chen # 1 2,  Zhaoyan Jiang # 1,  Wanxuan Song # 2,  Chuqiao Lu 2,  Yanbing Lin 3,  Shiyao Xu 2,  Kunxin Xie 4,  Li Wan 5,  Xiaoqin Yuan 6
Affiliations

Affiliations

  • 1 Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China.
  • 2 Department of Clinical Medicine, First Clinical Medicine College, Nanjing Medical University, Nanjing, 211166, China.
  • 3 Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China.
  • 4 Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, China.
  • 5 Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, 223302, China. doctorwl@njmu.edu.cn.
  • 6 Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China. yuanxq@njmu.edu.cn.
  • # Contributed equally.
PMID: 40340827 DOI: 10.1186/s12876-025-03918-8
Abstract

We identified a subset of patients with colorectal Cancer (CRC) enriched with "collagen-TAMs," designated the CM class, using large integrated colon Cancer transcriptome and single-cell transcriptome datasets. This classification system could be used as an extension of the traditional CMS classification system for CRC to guide more accurate classification and treatment.We also screened CAF-derived THBS2 as a potential biomarker for CM and found that it plays an important role in CRC disease models in vitro and in vivo, promoting tumor development and metastasis as well as TAM recruitment. Targeting THBS2 combined with PD-1 therapy effectively improved the therapeutic effect of immunotherapy in vivo. The CM classification provides a new perspective for CRC treatment, and THBS2, which is highly expressed in CM cases, can be used as a new potential combined target for immunotherapy.

Keywords

Classification system; Colorectal cancer; Immunotherapy; THBS2.

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