Targeted Drug Screening Leveraging Senescence-Induced T-Cell Exhaustion Signatures in Hepatocellular Carcinoma
Abstract
1. Introduction
2. Results
2.1. Construction of Human Hepatocellular Carcinoma T-Cell Profiles at Single-Cell Resolution
2.2. Differential Characterization of Aging and Young T Cell Subsets
2.3. Acquisition of a Set of Genes Highly Associated with Aging T-Cells
2.4. Establishment of a Stable and Effective Model of T-Cell Prognostic Exhaustion
2.5. High Levels of TERGs Are Associated with a Tumor-Suppressive Microenvironment
2.6. Clinical Applications of Exhaustion Models
2.7. Probing the Function of Five Prognostic Genes Associated with Senescent T-Cells
2.8. Molecular Docking of Prognostic Genes with Targeted Drugs
3. Discussion
4. Materials and Methods
4.1. Data Collection
4.2. Integration of Single-Cell Datasets, Standardization Process, and Cell Population Annotation
4.3. The ssGSEA Algorithm Categorizes T Cells into Aging and Young T Cells
4.4. Comparison of Different Properties of Aging and Young T-Cell Subsets
4.5. Screening of Gene Sets Highly Relevant to T-Cell Senescence
4.6. Cibersort Calculates the Abundance of Cell Types in a Sample
4.7. Modeling Prognostic Exhaustion
4.8. Functional Exploration of Prognostic Genes
4.9. Screening of Targeted Drugs
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
List of Abbreviations
HCC | Hepatocellular Carcinoma |
LIHC | Liver hepatocellular carcinoma |
TIME | Immune microenvironment |
scRNAseq | Single-cell RNA sequencing |
PT | primary hepatocellular carcinoma tumor |
PVTT | portal vein cancer thrombosis |
MLN | metastatic lymph node |
NLT | normal liver tissue |
TREGs | T-cell exhaustion-related genes |
GEO | Gene Expression Omnibus Database |
TCGA | The Cancer Genome Atlas |
GSEA | Gene Set Enrichment Analysis |
ROC | Receiver operating characteristic curve |
ssGSEA | Single sample Gene Set Enrichment Analysis |
GSVA | Gene set variation analysis |
CTD | Comparative Toxicogenomics Database |
Treg Cell | Regulatory T Cell |
Th17 | T helper type 17 cell |
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Qi, Q.; Pang, J.; Chen, Y.; Tang, Y.; Wang, H.; Gul, S.; Sun, Y.; Tang, W.; Sheng, M. Targeted Drug Screening Leveraging Senescence-Induced T-Cell Exhaustion Signatures in Hepatocellular Carcinoma. Int. J. Mol. Sci. 2024, 25, 11232. https://doi.org/10.3390/ijms252011232
Qi Q, Pang J, Chen Y, Tang Y, Wang H, Gul S, Sun Y, Tang W, Sheng M. Targeted Drug Screening Leveraging Senescence-Induced T-Cell Exhaustion Signatures in Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2024; 25(20):11232. https://doi.org/10.3390/ijms252011232
Chicago/Turabian StyleQi, Qi, Jianyu Pang, Yongzhi Chen, Yuheng Tang, Hui Wang, Samina Gul, Yingjie Sun, Wenru Tang, and Miaomiao Sheng. 2024. "Targeted Drug Screening Leveraging Senescence-Induced T-Cell Exhaustion Signatures in Hepatocellular Carcinoma" International Journal of Molecular Sciences 25, no. 20: 11232. https://doi.org/10.3390/ijms252011232
APA StyleQi, Q., Pang, J., Chen, Y., Tang, Y., Wang, H., Gul, S., Sun, Y., Tang, W., & Sheng, M. (2024). Targeted Drug Screening Leveraging Senescence-Induced T-Cell Exhaustion Signatures in Hepatocellular Carcinoma. International Journal of Molecular Sciences, 25(20), 11232. https://doi.org/10.3390/ijms252011232