Identification of biomarkers associated with exhausted CD8 + T cells in the tumor microenvironment of intrahepatic cholangiocarcinoma based on Mendelian randomization and bioinformatics analysis
Abstract Intrahepatic cholangiocarcinoma (iCCA) represents a growing health concern due to its increasing incidence and poor prognosis, highlighting the urgent need for biomarkers and therapeutic targets. This study utilized BayesPrism deconvolution, Weighted Gene Co-expression Network Analysis (WGC...
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| Format: | Article |
| Language: | English |
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Springer
2025-06-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02970-w |
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| author | LiuXing Feng Quan Yuan Hao Yu RongJie Ye ZhenHao Xie JiaHuan Xu XiuDong Li ShuangJia Wang |
| author_facet | LiuXing Feng Quan Yuan Hao Yu RongJie Ye ZhenHao Xie JiaHuan Xu XiuDong Li ShuangJia Wang |
| author_sort | LiuXing Feng |
| collection | DOAJ |
| description | Abstract Intrahepatic cholangiocarcinoma (iCCA) represents a growing health concern due to its increasing incidence and poor prognosis, highlighting the urgent need for biomarkers and therapeutic targets. This study utilized BayesPrism deconvolution, Weighted Gene Co-expression Network Analysis (WGCNA), and Summary Mendelian Randomization (SMR), integrated with single-cell RNA sequencing (scRNA-seq) data, to analyze the tumor microenvironment. Seven distinct cell subpopulations, including Exhausted CD8 + T cells (Tex), were identified. Notably, scPagwas analysis revealed gene enrichment in UQCRH, HINT1, and AKR1C3, associated with Tex. BayesPrism analysis confirmed their increased presence in the tumor microenvironment, indicating a role in immune evasion. WGCNA identified 594 genes linked to these cells, with PNO1 and AKR1C5P emerging as potential disease-associated genes. These findings highlight the critical role of Tex in immune suppression and identify key genes for further investigation in iCCA progression and treatment strategies. |
| format | Article |
| id | doaj-art-8f9f01e1487d4cd6af5b250b2edf5e1c |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-8f9f01e1487d4cd6af5b250b2edf5e1c2025-08-20T03:45:31ZengSpringerDiscover Oncology2730-60112025-06-0116111810.1007/s12672-025-02970-wIdentification of biomarkers associated with exhausted CD8 + T cells in the tumor microenvironment of intrahepatic cholangiocarcinoma based on Mendelian randomization and bioinformatics analysisLiuXing Feng0Quan Yuan1Hao Yu2RongJie Ye3ZhenHao Xie4JiaHuan Xu5XiuDong Li6ShuangJia Wang7Department of Hepato-Biliary-Pancreatic and Vascular Surgery, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen UniversityHarbin Medical University Cancer HospitalDepartment of Hepato-Biliary-Pancreatic and Vascular Surgery, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen UniversityDepartment of Orthopaedics, Quanzhou First Hospital Affiliated to Fujian Medical UniversityDepartment of Orthopaedics, Quanzhou First Hospital Affiliated to Fujian Medical UniversityDepartment of Basic Medical Sciences, Putian UniversityDepartment of Hepato-Biliary-Pancreatic and Vascular Surgery, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen UniversityDepartment of Hepato-Biliary-Pancreatic and Vascular Surgery, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen UniversityAbstract Intrahepatic cholangiocarcinoma (iCCA) represents a growing health concern due to its increasing incidence and poor prognosis, highlighting the urgent need for biomarkers and therapeutic targets. This study utilized BayesPrism deconvolution, Weighted Gene Co-expression Network Analysis (WGCNA), and Summary Mendelian Randomization (SMR), integrated with single-cell RNA sequencing (scRNA-seq) data, to analyze the tumor microenvironment. Seven distinct cell subpopulations, including Exhausted CD8 + T cells (Tex), were identified. Notably, scPagwas analysis revealed gene enrichment in UQCRH, HINT1, and AKR1C3, associated with Tex. BayesPrism analysis confirmed their increased presence in the tumor microenvironment, indicating a role in immune evasion. WGCNA identified 594 genes linked to these cells, with PNO1 and AKR1C5P emerging as potential disease-associated genes. These findings highlight the critical role of Tex in immune suppression and identify key genes for further investigation in iCCA progression and treatment strategies.https://doi.org/10.1007/s12672-025-02970-wIntrahepatic cholangiocarcinomaExhausted CD8 + T cellsImmunotherapyMendelian randomization |
| spellingShingle | LiuXing Feng Quan Yuan Hao Yu RongJie Ye ZhenHao Xie JiaHuan Xu XiuDong Li ShuangJia Wang Identification of biomarkers associated with exhausted CD8 + T cells in the tumor microenvironment of intrahepatic cholangiocarcinoma based on Mendelian randomization and bioinformatics analysis Discover Oncology Intrahepatic cholangiocarcinoma Exhausted CD8 + T cells Immunotherapy Mendelian randomization |
| title | Identification of biomarkers associated with exhausted CD8 + T cells in the tumor microenvironment of intrahepatic cholangiocarcinoma based on Mendelian randomization and bioinformatics analysis |
| title_full | Identification of biomarkers associated with exhausted CD8 + T cells in the tumor microenvironment of intrahepatic cholangiocarcinoma based on Mendelian randomization and bioinformatics analysis |
| title_fullStr | Identification of biomarkers associated with exhausted CD8 + T cells in the tumor microenvironment of intrahepatic cholangiocarcinoma based on Mendelian randomization and bioinformatics analysis |
| title_full_unstemmed | Identification of biomarkers associated with exhausted CD8 + T cells in the tumor microenvironment of intrahepatic cholangiocarcinoma based on Mendelian randomization and bioinformatics analysis |
| title_short | Identification of biomarkers associated with exhausted CD8 + T cells in the tumor microenvironment of intrahepatic cholangiocarcinoma based on Mendelian randomization and bioinformatics analysis |
| title_sort | identification of biomarkers associated with exhausted cd8 t cells in the tumor microenvironment of intrahepatic cholangiocarcinoma based on mendelian randomization and bioinformatics analysis |
| topic | Intrahepatic cholangiocarcinoma Exhausted CD8 + T cells Immunotherapy Mendelian randomization |
| url | https://doi.org/10.1007/s12672-025-02970-w |
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