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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Main Authors: LiuXing Feng, Quan Yuan, Hao Yu, RongJie Ye, ZhenHao Xie, JiaHuan Xu, XiuDong Li, ShuangJia Wang
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02970-w
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Summary: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.
ISSN:2730-6011