Cancer-associated fibroblasts gene signature: a novel approach to survival prediction and immunotherapy guidance in colon cancer
BackgroundFibroblasts 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.MethodsWe identified fibroblast-associated specific marker genes in co...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1532306/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850186588722561024 |
|---|---|
| author | Wenbing Zhang Chi Yang Ye Lu Ye Lu Chenling Tang Mengyu Zhao Zhaohui Wang Jidong Gao Jidong Gao Shuangjiu Hu Zhihua Chen |
| author_facet | Wenbing Zhang Chi Yang Ye Lu Ye Lu Chenling Tang Mengyu Zhao Zhaohui Wang Jidong Gao Jidong Gao Shuangjiu Hu Zhihua Chen |
| author_sort | Wenbing Zhang |
| collection | DOAJ |
| description | BackgroundFibroblasts 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.MethodsWe 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 high-risk and low-risk cohorts based on the median risk score. Additionally, the impact of 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.ResultsRelying 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.ConclusionOur 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. |
| format | Article |
| id | doaj-art-6c7fb5cff84d46d38c417806102af60d |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-6c7fb5cff84d46d38c417806102af60d2025-08-20T02:16:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15323061532306Cancer-associated fibroblasts gene signature: a novel approach to survival prediction and immunotherapy guidance in colon cancerWenbing Zhang0Chi Yang1Ye Lu2Ye Lu3Chenling Tang4Mengyu Zhao5Zhaohui Wang6Jidong Gao7Jidong Gao8Shuangjiu Hu9Zhihua Chen10Department of General Surgery, Anqing First People’s Hospital of Anhui Medical University, Anqing, ChinaDepartment of General Surgery, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, QingPu District Central Hospital Shanghai, No. 1158, Gong Yuan Dong Road, Shanghai, ChinaDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, ChinaThe First People’s Hospital of Taicang City, Taicang Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of General Surgery, Anqing First People’s Hospital of Anhui Medical University, Anqing, ChinaDepartment of General Surgery, Anqing First People’s Hospital of Anhui Medical University, Anqing, ChinaDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, ChinaDepartment of General Surgery, Anqing First People’s Hospital of Anhui Medical University, Anqing, ChinaThe First People’s Hospital of Taicang City, Taicang Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaBackgroundFibroblasts 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.MethodsWe 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 high-risk and low-risk cohorts based on the median risk score. Additionally, the impact of 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.ResultsRelying 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1532306/fullcolon adenocarcinomacancer-associated fibroblastssignaturetumor immune microenvironmentMAN1B1 |
| spellingShingle | Wenbing Zhang Chi Yang Ye Lu Ye Lu Chenling Tang Mengyu Zhao Zhaohui Wang Jidong Gao Jidong Gao Shuangjiu Hu Zhihua Chen Cancer-associated fibroblasts gene signature: a novel approach to survival prediction and immunotherapy guidance in colon cancer Frontiers in Immunology colon adenocarcinoma cancer-associated fibroblasts signature tumor immune microenvironment MAN1B1 |
| title | Cancer-associated fibroblasts gene signature: a novel approach to survival prediction and immunotherapy guidance in colon cancer |
| title_full | Cancer-associated fibroblasts gene signature: a novel approach to survival prediction and immunotherapy guidance in colon cancer |
| title_fullStr | Cancer-associated fibroblasts gene signature: a novel approach to survival prediction and immunotherapy guidance in colon cancer |
| title_full_unstemmed | Cancer-associated fibroblasts gene signature: a novel approach to survival prediction and immunotherapy guidance in colon cancer |
| title_short | Cancer-associated fibroblasts gene signature: a novel approach to survival prediction and immunotherapy guidance in colon cancer |
| title_sort | cancer associated fibroblasts gene signature a novel approach to survival prediction and immunotherapy guidance in colon cancer |
| topic | colon adenocarcinoma cancer-associated fibroblasts signature tumor immune microenvironment MAN1B1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1532306/full |
| work_keys_str_mv | AT wenbingzhang cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT chiyang cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT yelu cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT yelu cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT chenlingtang cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT mengyuzhao cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT zhaohuiwang cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT jidonggao cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT jidonggao cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT shuangjiuhu cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer AT zhihuachen cancerassociatedfibroblastsgenesignatureanovelapproachtosurvivalpredictionandimmunotherapyguidanceincoloncancer |