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

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 c...

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Main Authors: Shuwen Chen, Zhaoyan Jiang, Wanxuan Song, Chuqiao Lu, Yanbing Lin, Shiyao Xu, Kunxin Xie, Li Wan, Xiaoqin Yuan
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Gastroenterology
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Online Access:https://doi.org/10.1186/s12876-025-03918-8
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author Shuwen Chen
Zhaoyan Jiang
Wanxuan Song
Chuqiao Lu
Yanbing Lin
Shiyao Xu
Kunxin Xie
Li Wan
Xiaoqin Yuan
author_facet Shuwen Chen
Zhaoyan Jiang
Wanxuan Song
Chuqiao Lu
Yanbing Lin
Shiyao Xu
Kunxin Xie
Li Wan
Xiaoqin Yuan
author_sort Shuwen Chen
collection DOAJ
description 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.
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issn 1471-230X
language English
publishDate 2025-05-01
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series BMC Gastroenterology
spelling doaj-art-b618a15c932d4c0fb616b68fca86851b2025-08-20T03:09:19ZengBMCBMC Gastroenterology1471-230X2025-05-0125111810.1186/s12876-025-03918-8Identification of the "Collagen-Macrophage" sub-category of patients with colorectal cancer as an extension of the CMS4 subtype with THBS2 as a therapeutic targetShuwen Chen0Zhaoyan Jiang1Wanxuan Song2Chuqiao Lu3Yanbing Lin4Shiyao Xu5Kunxin Xie6Li Wan7Xiaoqin Yuan8Department of Anatomy, Histology and Embryology, Nanjing Medical UniversityDepartment of Anatomy, Histology and Embryology, Nanjing Medical UniversityDepartment of Clinical Medicine, First Clinical Medicine College, Nanjing Medical UniversityDepartment of Clinical Medicine, First Clinical Medicine College, Nanjing Medical UniversityResearch Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Clinical Medicine, First Clinical Medicine College, Nanjing Medical UniversityDepartment of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical UniversityDepartment of Oncology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical UniversityDepartment of Anatomy, Histology and Embryology, Nanjing Medical UniversityAbstract 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.https://doi.org/10.1186/s12876-025-03918-8Colorectal cancerImmunotherapyClassification systemTHBS2
spellingShingle Shuwen Chen
Zhaoyan Jiang
Wanxuan Song
Chuqiao Lu
Yanbing Lin
Shiyao Xu
Kunxin Xie
Li Wan
Xiaoqin Yuan
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 Gastroenterology
Colorectal cancer
Immunotherapy
Classification system
THBS2
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Colorectal cancer
Immunotherapy
Classification system
THBS2
url https://doi.org/10.1186/s12876-025-03918-8
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