Identification of a Cancer Stem Cell-Related Gene Signature in Hepatocellular Carcinoma Based on Single-Cell RNA-Seq and Bulk RNA-Seq Analysis
Abstract
1. Introduction
2. Results
2.1. Identification of LIHC–Specific BCSC–Related Genes and Functional Analysis
2.2. Construction of a Prognostic Model Using DE-BCSCs
2.3. The Creation and Verification of a Nomogram Model
2.4. Identification of DEGs and Gene Set Enrichment Analysis (GSEA)
2.5. Elucidation of DE–BCSCs as Potential Protective Factors
2.6. The Distribution of Tumor-Infiltrating Immune Cells (TICs) Across Two Distinct Subgroups
2.7. The Single-Cell Analysis Predicts the Expression Distribution of Model Genes and Intercellular Communication
2.8. Sensitivity Analysis of Potential Clinical Drugs Within Groups Identified as High-Risk and Low-Risk
3. Discussion
4. Materials and Methods
4.1. Diagram of Study Flow and Data Collection
4.2. Identification of DE–BCSCs in LIHC
4.3. Designing and Validating Prognostic Models Based on DE–BCSCs
4.4. Examining How the Risk Score Can Help in Clinical Diagnosis
4.5. How Prognostic DE–BCSCs Influence Immune Cell Infiltration in Tumors
4.6. Prediction of Chemotherapy Susceptibility
4.7. ScRNA and Cell Communication Analysis of the GSE156625 Data Set
4.8. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CSCs | Cancer stem cells |
BCSCs | Biomarkers of CSCs |
DE–BCSCs | Differentially expressed BCSCs |
TCGA | The Cancer Genome Atlas |
ICGC | International Cancer Genome Consortium |
GEO | Gene Expression Omnibus |
scRNA-seq | single-cell RNA sequencing |
GO | Gene Ontology |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
LASSO | Least Absolute Shrinkage and Selection Operator |
OS | Overall Survival |
TME | Tumor microenvironment |
LIHC | Liver hepatocellular carcinoma |
HCC | Hepatocellular carcinoma |
EMT | Epithelial Mesenchymal Transition |
UMAP | Uniform Manifold Approximation and Projection |
TNM | Tumor Node Metastasis |
TICs | Tumor-Infiltrating Immune Cells |
GSEA | Gene Set Enrichment Analysis |
LIANA | LIgand-receptor ANalysis frAmework |
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Wu, J.; Liu, X.; Huang, S.; Liu, W. Identification of a Cancer Stem Cell-Related Gene Signature in Hepatocellular Carcinoma Based on Single-Cell RNA-Seq and Bulk RNA-Seq Analysis. Int. J. Mol. Sci. 2025, 26, 2933. https://doi.org/10.3390/ijms26072933
Wu J, Liu X, Huang S, Liu W. Identification of a Cancer Stem Cell-Related Gene Signature in Hepatocellular Carcinoma Based on Single-Cell RNA-Seq and Bulk RNA-Seq Analysis. International Journal of Molecular Sciences. 2025; 26(7):2933. https://doi.org/10.3390/ijms26072933
Chicago/Turabian StyleWu, Jing, Xu Liu, Sheng Huang, and Wei Liu. 2025. "Identification of a Cancer Stem Cell-Related Gene Signature in Hepatocellular Carcinoma Based on Single-Cell RNA-Seq and Bulk RNA-Seq Analysis" International Journal of Molecular Sciences 26, no. 7: 2933. https://doi.org/10.3390/ijms26072933
APA StyleWu, J., Liu, X., Huang, S., & Liu, W. (2025). Identification of a Cancer Stem Cell-Related Gene Signature in Hepatocellular Carcinoma Based on Single-Cell RNA-Seq and Bulk RNA-Seq Analysis. International Journal of Molecular Sciences, 26(7), 2933. https://doi.org/10.3390/ijms26072933