Development of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seq
Abstract Low immune infiltration is closely associated with poor clinical results and an unfavorable response to therapy in triple-negative breast cancer (TNBC). T-cell exhaustion (TEX) is a significant risk factor for tumor immunosuppression and invasion. Although improving TEX and enhancing effect...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-01812-z |
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| _version_ | 1823861856049037312 |
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| author | Yulin Shi Yang Yu Jiahan Zhao Linan Huang Qingyang Wang Qi Sun Lijuan Liu Changgang Sun |
| author_facet | Yulin Shi Yang Yu Jiahan Zhao Linan Huang Qingyang Wang Qi Sun Lijuan Liu Changgang Sun |
| author_sort | Yulin Shi |
| collection | DOAJ |
| description | Abstract Low immune infiltration is closely associated with poor clinical results and an unfavorable response to therapy in triple-negative breast cancer (TNBC). T-cell exhaustion (TEX) is a significant risk factor for tumor immunosuppression and invasion. Although improving TEX and enhancing effector function are promising strategies for strengthening immunotherapy, their role in the pathogenesis of TNBC remains unclear. This study’s objective was to develop a prognostic model for TNBC based on exhausted CD8+ T-cell (CD8+ Tex)-related differentially expressed genes (DEGs) and to investigate its clinical and immune relevance. Initially, 398 CD8+ Tex-related genes were screened utilizing single-cell RNA sequencing (scRNA-seq) data from TNBC patients. Pseudotime analysis confirmed that CD8+ Tex mainly clustered at the end of the differentiation pathways, making them a critical subset in TNBC progression. By analyzing the TCGA cohort, ten CD8+ Tex-related DEGs were identified as significantly correlated with overall survival (OS) in TNBC patients, and a prognostic model containing four biomarkers (GBP1, CTSD, ABHD14B, and HLA-A) was constructed. The model demonstrated robust predictive capability in both the TCGA cohort and an external cohort, with the low-risk group exhibiting elevated expression of immunological checkpoint molecules and immune cell infiltration, as well as better responses to immunotherapy and chemotherapy. Furthermore, these four biomarkers were found to be highly expressed on CD8+ Tex and were associated with cellular communication efficiency. Therefore, this model is expected to be a new method for forecasting TNBC patients’ prognosis and effectiveness of treatment, providing new insights for clinical decision-making. |
| format | Article |
| id | doaj-art-f67b3cb7c696429da4e859238a365b79 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-f67b3cb7c696429da4e859238a365b792025-02-09T12:43:27ZengSpringerDiscover Oncology2730-60112025-02-0116111810.1007/s12672-025-01812-zDevelopment of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seqYulin Shi0Yang Yu1Jiahan Zhao2Linan Huang3Qingyang Wang4Qi Sun5Lijuan Liu6Changgang Sun7College of First Clinical Medicine, Shandong University of Traditional Chinese MedicineState Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and TechnologyCollege of First Clinical Medicine, Shandong University of Traditional Chinese MedicineCollege of Traditional Chinese Medicine, Shandong Second Medical UniversityCollege of First Clinical Medicine, Shandong University of Traditional Chinese MedicineCollege of First Clinical Medicine, Shandong University of Traditional Chinese MedicineDepartment of Oncology, Weifang Traditional Chinese HospitalCollege of Traditional Chinese Medicine, Shandong Second Medical UniversityAbstract Low immune infiltration is closely associated with poor clinical results and an unfavorable response to therapy in triple-negative breast cancer (TNBC). T-cell exhaustion (TEX) is a significant risk factor for tumor immunosuppression and invasion. Although improving TEX and enhancing effector function are promising strategies for strengthening immunotherapy, their role in the pathogenesis of TNBC remains unclear. This study’s objective was to develop a prognostic model for TNBC based on exhausted CD8+ T-cell (CD8+ Tex)-related differentially expressed genes (DEGs) and to investigate its clinical and immune relevance. Initially, 398 CD8+ Tex-related genes were screened utilizing single-cell RNA sequencing (scRNA-seq) data from TNBC patients. Pseudotime analysis confirmed that CD8+ Tex mainly clustered at the end of the differentiation pathways, making them a critical subset in TNBC progression. By analyzing the TCGA cohort, ten CD8+ Tex-related DEGs were identified as significantly correlated with overall survival (OS) in TNBC patients, and a prognostic model containing four biomarkers (GBP1, CTSD, ABHD14B, and HLA-A) was constructed. The model demonstrated robust predictive capability in both the TCGA cohort and an external cohort, with the low-risk group exhibiting elevated expression of immunological checkpoint molecules and immune cell infiltration, as well as better responses to immunotherapy and chemotherapy. Furthermore, these four biomarkers were found to be highly expressed on CD8+ Tex and were associated with cellular communication efficiency. Therefore, this model is expected to be a new method for forecasting TNBC patients’ prognosis and effectiveness of treatment, providing new insights for clinical decision-making.https://doi.org/10.1007/s12672-025-01812-zExhausted CD8+ T cellTriple-negative breast cancerSingle-cell RNA sequencingCellular communicationTumor immune microenvironment |
| spellingShingle | Yulin Shi Yang Yu Jiahan Zhao Linan Huang Qingyang Wang Qi Sun Lijuan Liu Changgang Sun Development of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seq Discover Oncology Exhausted CD8+ T cell Triple-negative breast cancer Single-cell RNA sequencing Cellular communication Tumor immune microenvironment |
| title | Development of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seq |
| title_full | Development of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seq |
| title_fullStr | Development of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seq |
| title_full_unstemmed | Development of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seq |
| title_short | Development of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seq |
| title_sort | development of a prognostic model based on four genes related to exhausted cd8 t cell in triple negative breast cancer patients a comprehensive analysis integrating scrna seq and bulk rna seq |
| topic | Exhausted CD8+ T cell Triple-negative breast cancer Single-cell RNA sequencing Cellular communication Tumor immune microenvironment |
| url | https://doi.org/10.1007/s12672-025-01812-z |
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