A Novel Molecular Signature of Cancer-Associated Fibroblasts Predicts Prognosis and Immunotherapy Response in Pancreatic Cancer
Abstract
:1. Introduction
2. Results
2.1. α-SMA+ CAFs Accumulate in PC Tissues with Worse Prognoses
2.2. Genetic Mutation Landscape of CRGs in PC
2.3. Identification of CAF Subtypes and Characteristics of the TME in PC
2.4. Establishment and Verification of the Prognostic CRG Score
2.5. Characteristics of the TME and Function Enrichment in Distinct Subgroups
2.6. Association of the CRG Score with Tumor Mutation Burden (TMB) and Mutation
2.7. Clinical Outcomes and Drug Susceptibility Analysis
2.8. Protein Expression Level of CAF-Related Risk Genes and Survival Analysis
3. Discussion
4. Materials and Methods
4.1. Human Tissue Specimens
4.2. Cell Lines and Mouse Pancreatic Cancer Model
4.3. Masson’s Trichrome Staining
4.4. Immunohistochemistry and Tissue Microarrays
4.5. Flow Cytometry Analysis
4.6. PC Transcriptome Data Sources
4.7. Consensus Clustering Analysis of CRGs
4.8. Correlations of Molecular Patterns with the Clinical Features and Prognosis of PC
4.9. Association of Molecular Subtypes with Tumor Immune Microenvironment of PC
4.10. Relationship of CAF Subtypes with Immunotherapy Responses in PC
4.11. Development of the CAF-Related Gene Risk Signature
4.12. Expression Level Validation of CAF-Related Risk Gene Expression
4.13. Identification of Immune Microenvironment Affected by CRGs
4.14. Correlation of CRG Score Signature with Signal Pathways, Tumor Mutation, and Chemosensitivity
4.15. Additional Bioinformatics and Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ge, W.; Yue, M.; Wang, Y.; Wang, Y.; Xue, S.; Shentu, D.; Mao, T.; Zhang, X.; Xu, H.; Li, S.; et al. A Novel Molecular Signature of Cancer-Associated Fibroblasts Predicts Prognosis and Immunotherapy Response in Pancreatic Cancer. Int. J. Mol. Sci. 2023, 24, 156. https://doi.org/10.3390/ijms24010156
Ge W, Yue M, Wang Y, Wang Y, Xue S, Shentu D, Mao T, Zhang X, Xu H, Li S, et al. A Novel Molecular Signature of Cancer-Associated Fibroblasts Predicts Prognosis and Immunotherapy Response in Pancreatic Cancer. International Journal of Molecular Sciences. 2023; 24(1):156. https://doi.org/10.3390/ijms24010156
Chicago/Turabian StyleGe, Weiyu, Ming Yue, Yanling Wang, Yongchao Wang, Shengbai Xue, Daiyuan Shentu, Tiebo Mao, Xiaofei Zhang, Haiyan Xu, Shumin Li, and et al. 2023. "A Novel Molecular Signature of Cancer-Associated Fibroblasts Predicts Prognosis and Immunotherapy Response in Pancreatic Cancer" International Journal of Molecular Sciences 24, no. 1: 156. https://doi.org/10.3390/ijms24010156