Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma
IntroductionTo better understand the role of immune escape and cancer-associated fibroblasts (CAFs) in colon adenocarcinoma (COAD), an integrative analysis of the tumor microenvironment was performed using a set of 12 immune- and CAF-related genes (ICRGs).MethodsUnivariate and least absolute shrinka...
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Frontiers Media S.A.
2024-01-01
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| author | Jingsun Wei Jingsun Wei Jingsun Wei Xiaoxu Ge Xiaoxu Ge Xiaoxu Ge Yucheng Qian Yucheng Qian Yucheng Qian Kai Jiang Kai Jiang Kai Jiang Xin Chen Xin Chen Xin Chen Wei Lu Wei Lu Wei Lu Hang Yang Hang Yang Hang Yang Dongliang Fu Dongliang Fu Dongliang Fu Yimin Fang Yimin Fang Yimin Fang Xinyi Zhou Xinyi Zhou Xinyi Zhou Qian Xiao Qian Xiao Qian Xiao Yang Tang Yang Tang Yang Tang Kefeng Ding Kefeng Ding Kefeng Ding |
| author_facet | Jingsun Wei Jingsun Wei Jingsun Wei Xiaoxu Ge Xiaoxu Ge Xiaoxu Ge Yucheng Qian Yucheng Qian Yucheng Qian Kai Jiang Kai Jiang Kai Jiang Xin Chen Xin Chen Xin Chen Wei Lu Wei Lu Wei Lu Hang Yang Hang Yang Hang Yang Dongliang Fu Dongliang Fu Dongliang Fu Yimin Fang Yimin Fang Yimin Fang Xinyi Zhou Xinyi Zhou Xinyi Zhou Qian Xiao Qian Xiao Qian Xiao Yang Tang Yang Tang Yang Tang Kefeng Ding Kefeng Ding Kefeng Ding |
| author_sort | Jingsun Wei |
| collection | DOAJ |
| description | IntroductionTo better understand the role of immune escape and cancer-associated fibroblasts (CAFs) in colon adenocarcinoma (COAD), an integrative analysis of the tumor microenvironment was performed using a set of 12 immune- and CAF-related genes (ICRGs).MethodsUnivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to establish a prognostic signature based on the expression of these 12 genes (S1PR5, AEN, IL20RB, FGF9, OSBPL1A, HSF4, PCAT6, FABP4, KIF15, ZNF792, CD1B and GLP2R). This signature was validated in both internal and external cohorts and was found to have a higher C-index than previous COAD signatures, confirming its robustness and reliability. To make use of this signature in clinical settings, a nomogram incorporating ICRG signatures and key clinical parameters, such as age and T stage, was developed. Finally, the role of S1PR5 in the immune response of COAD was validated through in vitro cytotoxicity experiments.ResultsThe developed nomogram exhibited slightly improved predictive accuracy compared to the ICRG signature alone, as indicated by the areas under the receiver operating characteristic curves (AUC, nomogram:0.838; ICRGs:0.807). The study also evaluated the relationships between risk scores (RS) based on the expression of the ICRGs and other key immunotherapy variables, including immune checkpoint expression, immunophenoscore (IPS), and microsatellite instability (MSI). Integration of these variables led to more precise prediction of treatment efficacy, enabling personalized immunotherapy for COAD patients. Knocking down S1PR5 can enhance the efficacy of PD-1 monoclonal antibody, promoting the cytotoxicity of T cells against HCT116 cells ((p<0.05).DiscussionThese findings indicate that the ICRG signature may be a valuable tool for predicting prognostic risk, evaluating the efficacy of immunotherapy, and tailoring personalized treatment options for patients with COAD. |
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| last_indexed | 2024-03-08T13:03:42Z |
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| spelling | doaj.art-e1d3281eba6d482288dd0d3ad2a6a9c52024-01-19T04:23:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011510.3389/fimmu.2024.12919381291938Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinomaJingsun Wei0Jingsun Wei1Jingsun Wei2Xiaoxu Ge3Xiaoxu Ge4Xiaoxu Ge5Yucheng Qian6Yucheng Qian7Yucheng Qian8Kai Jiang9Kai Jiang10Kai Jiang11Xin Chen12Xin Chen13Xin Chen14Wei Lu15Wei Lu16Wei Lu17Hang Yang18Hang Yang19Hang Yang20Dongliang Fu21Dongliang Fu22Dongliang Fu23Yimin Fang24Yimin Fang25Yimin Fang26Xinyi Zhou27Xinyi Zhou28Xinyi Zhou29Qian Xiao30Qian Xiao31Qian Xiao32Yang Tang33Yang Tang34Yang Tang35Kefeng Ding36Kefeng Ding37Kefeng Ding38Department of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, ChinaDepartment of Colorectal Surgery and Oncology, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, ChinaIntroductionTo better understand the role of immune escape and cancer-associated fibroblasts (CAFs) in colon adenocarcinoma (COAD), an integrative analysis of the tumor microenvironment was performed using a set of 12 immune- and CAF-related genes (ICRGs).MethodsUnivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to establish a prognostic signature based on the expression of these 12 genes (S1PR5, AEN, IL20RB, FGF9, OSBPL1A, HSF4, PCAT6, FABP4, KIF15, ZNF792, CD1B and GLP2R). This signature was validated in both internal and external cohorts and was found to have a higher C-index than previous COAD signatures, confirming its robustness and reliability. To make use of this signature in clinical settings, a nomogram incorporating ICRG signatures and key clinical parameters, such as age and T stage, was developed. Finally, the role of S1PR5 in the immune response of COAD was validated through in vitro cytotoxicity experiments.ResultsThe developed nomogram exhibited slightly improved predictive accuracy compared to the ICRG signature alone, as indicated by the areas under the receiver operating characteristic curves (AUC, nomogram:0.838; ICRGs:0.807). The study also evaluated the relationships between risk scores (RS) based on the expression of the ICRGs and other key immunotherapy variables, including immune checkpoint expression, immunophenoscore (IPS), and microsatellite instability (MSI). Integration of these variables led to more precise prediction of treatment efficacy, enabling personalized immunotherapy for COAD patients. Knocking down S1PR5 can enhance the efficacy of PD-1 monoclonal antibody, promoting the cytotoxicity of T cells against HCT116 cells ((p<0.05).DiscussionThese findings indicate that the ICRG signature may be a valuable tool for predicting prognostic risk, evaluating the efficacy of immunotherapy, and tailoring personalized treatment options for patients with COAD.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1291938/fullimmuneCAFprognosiscolon adenocarcinomaTME |
| spellingShingle | Jingsun Wei Jingsun Wei Jingsun Wei Xiaoxu Ge Xiaoxu Ge Xiaoxu Ge Yucheng Qian Yucheng Qian Yucheng Qian Kai Jiang Kai Jiang Kai Jiang Xin Chen Xin Chen Xin Chen Wei Lu Wei Lu Wei Lu Hang Yang Hang Yang Hang Yang Dongliang Fu Dongliang Fu Dongliang Fu Yimin Fang Yimin Fang Yimin Fang Xinyi Zhou Xinyi Zhou Xinyi Zhou Qian Xiao Qian Xiao Qian Xiao Yang Tang Yang Tang Yang Tang Kefeng Ding Kefeng Ding Kefeng Ding Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma Frontiers in Immunology immune CAF prognosis colon adenocarcinoma TME |
| title | Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma |
| title_full | Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma |
| title_fullStr | Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma |
| title_full_unstemmed | Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma |
| title_short | Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma |
| title_sort | development and verification of a combined immune and cancer associated fibroblast related prognostic signature for colon adenocarcinoma |
| topic | immune CAF prognosis colon adenocarcinoma TME |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1291938/full |
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