Development and Validation of a TNF Family-Based Signature for Predicting Prognosis, Tumor Immune Characteristics, and Immunotherapy Response in Colorectal Cancer Patients
In this study, a comprehensive analysis of TNF family members in colorectal cancer (CRC) was conducted and a TNF family-based signature (TFS) was generated to predict prognosis and immunotherapy response. Using the expression data of 516 CRC patients from The Cancer Genome Atlas (TCGA) database, TNF...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/6439975 |
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| author | Zheng Xiao Kechao Nie Tong Han Lin Cheng Zheyu Zhang Weijun Peng Dazun Shi |
| author_facet | Zheng Xiao Kechao Nie Tong Han Lin Cheng Zheyu Zhang Weijun Peng Dazun Shi |
| author_sort | Zheng Xiao |
| collection | DOAJ |
| description | In this study, a comprehensive analysis of TNF family members in colorectal cancer (CRC) was conducted and a TNF family-based signature (TFS) was generated to predict prognosis and immunotherapy response. Using the expression data of 516 CRC patients from The Cancer Genome Atlas (TCGA) database, TNF family members were screened to construct a TFS by using the univariate Cox proportional hazards regression and the least absolute shrinkage and selection operator- (LASSO-) Cox proportional hazards regression method. The TFS was then validated in a meta-Gene Expression Omnibus (GEO) cohort (n=1162) from the GEO database. Additionally, the tumor immune characteristics and predicted responses to immune checkpoint blockade in TFS-based risk subgroups were analyzed. Eight genes (TNFRSF11A, TNFRSF10C, TNFRSF10B, TNFSF11, TNFRSF25, TNFRSF19, LTBR, and NGFR) were used to construct the TFS. Compared to the high-risk patients, the low-risk patients had better overall survival, which was verified by the GEO data. In addition, a high TFS risk score was associated with high infiltration of regulatory T cells (Tregs), nonactivated macrophages (M0), natural killer cells, immune escape phenotypes, poor immunotherapy response, and tumorigenic and metastasis-related pathways. Conversely, a low TFS risk score was related to high infiltration of resting CD4 memory T cells and resting dendritic cells, few immune escape phenotypes, and high sensitivity to immunotherapy. Thus, the eight gene-based TFS is a promising index to predict the prognosis, immune characteristics, and immunotherapy response in CRC, and our results also provide new understanding of the role of the TNF family members in the prognosis and treatment of CRC. |
| format | Article |
| id | doaj-art-61ffb0015cb34e81af5a3238293f280c |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-61ffb0015cb34e81af5a3238293f280c2025-08-20T03:34:49ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/64399756439975Development and Validation of a TNF Family-Based Signature for Predicting Prognosis, Tumor Immune Characteristics, and Immunotherapy Response in Colorectal Cancer PatientsZheng Xiao0Kechao Nie1Tong Han2Lin Cheng3Zheyu Zhang4Weijun Peng5Dazun Shi6Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, ChinaDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, ChinaDepartment of General Surgery, The Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Changsha, Hunan 410011, ChinaDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, ChinaDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, ChinaDepartment of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, ChinaDepartment of Gynecology and Obstetrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaIn this study, a comprehensive analysis of TNF family members in colorectal cancer (CRC) was conducted and a TNF family-based signature (TFS) was generated to predict prognosis and immunotherapy response. Using the expression data of 516 CRC patients from The Cancer Genome Atlas (TCGA) database, TNF family members were screened to construct a TFS by using the univariate Cox proportional hazards regression and the least absolute shrinkage and selection operator- (LASSO-) Cox proportional hazards regression method. The TFS was then validated in a meta-Gene Expression Omnibus (GEO) cohort (n=1162) from the GEO database. Additionally, the tumor immune characteristics and predicted responses to immune checkpoint blockade in TFS-based risk subgroups were analyzed. Eight genes (TNFRSF11A, TNFRSF10C, TNFRSF10B, TNFSF11, TNFRSF25, TNFRSF19, LTBR, and NGFR) were used to construct the TFS. Compared to the high-risk patients, the low-risk patients had better overall survival, which was verified by the GEO data. In addition, a high TFS risk score was associated with high infiltration of regulatory T cells (Tregs), nonactivated macrophages (M0), natural killer cells, immune escape phenotypes, poor immunotherapy response, and tumorigenic and metastasis-related pathways. Conversely, a low TFS risk score was related to high infiltration of resting CD4 memory T cells and resting dendritic cells, few immune escape phenotypes, and high sensitivity to immunotherapy. Thus, the eight gene-based TFS is a promising index to predict the prognosis, immune characteristics, and immunotherapy response in CRC, and our results also provide new understanding of the role of the TNF family members in the prognosis and treatment of CRC.http://dx.doi.org/10.1155/2021/6439975 |
| spellingShingle | Zheng Xiao Kechao Nie Tong Han Lin Cheng Zheyu Zhang Weijun Peng Dazun Shi Development and Validation of a TNF Family-Based Signature for Predicting Prognosis, Tumor Immune Characteristics, and Immunotherapy Response in Colorectal Cancer Patients Journal of Immunology Research |
| title | Development and Validation of a TNF Family-Based Signature for Predicting Prognosis, Tumor Immune Characteristics, and Immunotherapy Response in Colorectal Cancer Patients |
| title_full | Development and Validation of a TNF Family-Based Signature for Predicting Prognosis, Tumor Immune Characteristics, and Immunotherapy Response in Colorectal Cancer Patients |
| title_fullStr | Development and Validation of a TNF Family-Based Signature for Predicting Prognosis, Tumor Immune Characteristics, and Immunotherapy Response in Colorectal Cancer Patients |
| title_full_unstemmed | Development and Validation of a TNF Family-Based Signature for Predicting Prognosis, Tumor Immune Characteristics, and Immunotherapy Response in Colorectal Cancer Patients |
| title_short | Development and Validation of a TNF Family-Based Signature for Predicting Prognosis, Tumor Immune Characteristics, and Immunotherapy Response in Colorectal Cancer Patients |
| title_sort | development and validation of a tnf family based signature for predicting prognosis tumor immune characteristics and immunotherapy response in colorectal cancer patients |
| url | http://dx.doi.org/10.1155/2021/6439975 |
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