Single-cell landscape of dynamic changes in CD8+ T cells, CD4+ T cells and exhausted T cells in hepatocellular carcinoma
Abstract Hepatocellular carcinoma has a high incidence and poor prognosis. In this study, we investigated the value of T-cell-related genes in prognosis by single-cell sequencing data in hepatocellular carcinoma. Twelve cases of hepatocellular carcinoma single-cell sequencing were included in the st...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88377-7 |
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| author | Rongqiang Liu Jing Ye Jianguo Wang Wangbin Ma Zhendong Qiu Jia Yu Weixing Wang |
| author_facet | Rongqiang Liu Jing Ye Jianguo Wang Wangbin Ma Zhendong Qiu Jia Yu Weixing Wang |
| author_sort | Rongqiang Liu |
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| description | Abstract Hepatocellular carcinoma has a high incidence and poor prognosis. In this study, we investigated the value of T-cell-related genes in prognosis by single-cell sequencing data in hepatocellular carcinoma. Twelve cases of hepatocellular carcinoma single-cell sequencing were included in the study. The high dimensional weighted gene co-expression network analysis (hdWGCNA) was used to identify gene modules associated with CD4+ T cells, CD8+ T cells and exhausted T cells. Altered signaling pathway activity in exhausted T cells was uncovered by the AUCell algorithm. xCELL, TIMER, QUANTISEQ, CIBERSORT and CIBERSORT-abs were performed to explore immune cell infiltration. Immune checkpoint inhibitor genes and TIDE methods were used to predict immunotherapy response. Finally, immunohistochemistry and real-time PCR were used to verify gene expression. The hdWGCNA algorithm identified 40 genes strongly associated with CD4+ T cells, CD8+ T cells and exhausted T cells. Seven genes were finally selected for transcriptome data modeling. The results of the three independent datasets suggested that the model had strong prognostic value. Model genes were critical factors influencing CD4+ T cell and CD8+ T cell infiltration in patients. The efficacy of PD-1 immunotherapy was higher in patients belonging to the low-risk group. Alterations in signaling pathways’ activity within exhausted T cells were crucial factors contributing to the decline in immune function. Differential expression of seven genes in CD8+ T cells, CD4+ T cells and exhausted T cells were key targets for improving immunotherapy response in HCC. |
| format | Article |
| id | doaj-art-acf75bceeaa4495d9529091905ed1e26 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-acf75bceeaa4495d9529091905ed1e262025-02-09T12:37:11ZengNature PortfolioScientific Reports2045-23222025-02-0115111210.1038/s41598-025-88377-7Single-cell landscape of dynamic changes in CD8+ T cells, CD4+ T cells and exhausted T cells in hepatocellular carcinomaRongqiang Liu0Jing Ye1Jianguo Wang2Wangbin Ma3Zhendong Qiu4Jia Yu5Weixing Wang6Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan UniversityAbstract Hepatocellular carcinoma has a high incidence and poor prognosis. In this study, we investigated the value of T-cell-related genes in prognosis by single-cell sequencing data in hepatocellular carcinoma. Twelve cases of hepatocellular carcinoma single-cell sequencing were included in the study. The high dimensional weighted gene co-expression network analysis (hdWGCNA) was used to identify gene modules associated with CD4+ T cells, CD8+ T cells and exhausted T cells. Altered signaling pathway activity in exhausted T cells was uncovered by the AUCell algorithm. xCELL, TIMER, QUANTISEQ, CIBERSORT and CIBERSORT-abs were performed to explore immune cell infiltration. Immune checkpoint inhibitor genes and TIDE methods were used to predict immunotherapy response. Finally, immunohistochemistry and real-time PCR were used to verify gene expression. The hdWGCNA algorithm identified 40 genes strongly associated with CD4+ T cells, CD8+ T cells and exhausted T cells. Seven genes were finally selected for transcriptome data modeling. The results of the three independent datasets suggested that the model had strong prognostic value. Model genes were critical factors influencing CD4+ T cell and CD8+ T cell infiltration in patients. The efficacy of PD-1 immunotherapy was higher in patients belonging to the low-risk group. Alterations in signaling pathways’ activity within exhausted T cells were crucial factors contributing to the decline in immune function. Differential expression of seven genes in CD8+ T cells, CD4+ T cells and exhausted T cells were key targets for improving immunotherapy response in HCC.https://doi.org/10.1038/s41598-025-88377-7Hepatocellular carcinomaSingle cellhdWGCNAImmunotherapy |
| spellingShingle | Rongqiang Liu Jing Ye Jianguo Wang Wangbin Ma Zhendong Qiu Jia Yu Weixing Wang Single-cell landscape of dynamic changes in CD8+ T cells, CD4+ T cells and exhausted T cells in hepatocellular carcinoma Scientific Reports Hepatocellular carcinoma Single cell hdWGCNA Immunotherapy |
| title | Single-cell landscape of dynamic changes in CD8+ T cells, CD4+ T cells and exhausted T cells in hepatocellular carcinoma |
| title_full | Single-cell landscape of dynamic changes in CD8+ T cells, CD4+ T cells and exhausted T cells in hepatocellular carcinoma |
| title_fullStr | Single-cell landscape of dynamic changes in CD8+ T cells, CD4+ T cells and exhausted T cells in hepatocellular carcinoma |
| title_full_unstemmed | Single-cell landscape of dynamic changes in CD8+ T cells, CD4+ T cells and exhausted T cells in hepatocellular carcinoma |
| title_short | Single-cell landscape of dynamic changes in CD8+ T cells, CD4+ T cells and exhausted T cells in hepatocellular carcinoma |
| title_sort | single cell landscape of dynamic changes in cd8 t cells cd4 t cells and exhausted t cells in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Single cell hdWGCNA Immunotherapy |
| url | https://doi.org/10.1038/s41598-025-88377-7 |
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