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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1532306
This article is part of the Research Topic Formation of Immunological Niches in Tumor Microenvironments: Mechanisms and Therapeutic Potential View all 22 articles
Cancer-associated Fibroblasts Genes Signature: A Novel Approach to Survival Prediction and Immunotherapy Guidance in Colon Cancer
Provisionally accepted
Wenbing Zhang 1,2
Chi Yang 3
Lu Ye 4 Chenling Tang 5
Mengyu Zhao 2
Zhaohui Wang 2
GAO JIDONG 4 Shuangjiu Hu 2
Zhihua Chen 5*- 1 Anhui Medical University, Hefei, China
- 2 Affiliated Anqing First People's Hospital of Anhui Medical University, Anqing, Anhui Province, China
- 3 Zhongshan Hospital Affiliated to Fudan University (QingPu Branch), Shanghai, Shanghai Municipality, China
- 4 Peking Union Medical College Hospital (CAMS), Beijing, Beijing Municipality, China
- 5 The First People's Hospital of Taicang, Taicang, China
Background: Fibroblasts can regulate tumour development by secreting various factors. For COAD survival prediction and CAFs-based treatment recommendations, it is critical to comprehend the heterogeneity of CAFs and find biomarkers.We identified fibroblast-associated specific marker genes in colon adenocarcinoma by single-cell sequencing analysis. A fibroblasts-related gene signature was developed, and colon adenocarcinoma patients were classified into highrisk and low-risk cohorts based on the median risk score. Additionally, the impact of CAFGs Signature in COAD these risk categories on the tumor microenvironment was evaluated. The ability of CAFGs signature to assess prognosis and guide treatment was validated using external cohorts. Ultimately, we verified MAN1B1 expression and function through in vitro assays.Results: Relying on the bulk RNA-seq and scRNA-seq data study, we created a predictive profile with 11 CAFGs. The profile effectively differentiated survival differences among cohorts of colon adenocarcinoma patients. The nomogram further effectively predicted the prognosis of COAD patients, with low-risk patients having a better prognosis. A higher immune infiltration rate and lower IC50 values of anticancer drugs were significant in the high-risk group. In cellular experiments, Following MAN1B1 knockdown, in cell assays, the colony formation, migration, and invasion ability of HCT116 and HT29 cell lines decreased.Our CAFG signature provides important insights into the role of CAF cells in influencing COAD prognosis. It may also serve as a guide for selecting immunotherapy options and predicting chemotherapy responses in COAD patients.
Keywords: Colon adenocarcinoma, cancer-associated fibroblasts, Signature, Tumor immune microenvironment, MAN1B1
Received: 21 Nov 2024; Accepted: 17 Mar 2025.
Copyright: © 2025 Zhang, Yang, Ye, Tang, Zhao, Wang, JIDONG, Hu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhihua Chen, The First People's Hospital of Taicang, Taicang, China
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