Integrated Analysis Revealed an Inflammatory Cancer-Associated Fibroblast-Based Subtypes with Promising Implications in Predicting the Prognosis and Immunotherapeutic Response of Bladder Cancer Patients
Abstract
:1. Introduction
2. Results
2.1. scRNA-seq Analysis Highlighted the Role of iCAFs in BCa
2.2. iCAF-Related Signature Dominated an Inflamed and Immunosuppressive TME of BCa
2.3. iCAF-Related Signature Stratified BCa into Molecular Subtypes with Distinct Biological Features
2.3.1. iCAF-related Subtypes had Distinct Immunogenomic Patterns
2.3.2. iCAF-related Subtypes had Distinct Dysregulated Pathways
2.3.3. iCAF-related Subtypes Hold Diverse Responses to Immunotherapy and Chemotherapy
2.4. iCAF-related Subtypes Demonstrated Robustness in the External GEO-meta Dataset
2.5. iCAF-related Subtypes Predicted Prognosis and Immunotherapeutic Response in ICI-Treated Cohorts
2.6. LOXL2+ iCAFs Predicted Poor Prognosis
2.7. Upregulated LOXL2 in CAFs Promoted the Proliferation, Migration, and Metastasis of BCa Cells
3. Discussion
4. Materials and Methods
4.1. Data Acquisition
4.2. iCAF-related Signature Identification
4.3. Enrichment Analyses
4.4. Unsupervised Clustering and Biological Properties Exploration
4.5. Hug Gene Identification
4.6. Cell Lines, Culture, Transfection, and Reagents
4.7. Quantitative Real-Time Reverse Transcription-Polymerase Chain Reaction (qRT-PCR)
4.8. Western Blotting and Antibodies
4.9. Conditioned Medium (CM) Derived from Fibroblasts
4.10. Cell Proliferation Assay
4.11. Wound-Healing and Transwell Assays
4.12. Enzyme-Linked Immunosorbent Assay (ELISA)
4.13. RNA-seq and Analyses
4.14. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Chen, H.; Yang, W.; Xue, X.; Li, Y.; Jin, Z.; Ji, Z. Integrated Analysis Revealed an Inflammatory Cancer-Associated Fibroblast-Based Subtypes with Promising Implications in Predicting the Prognosis and Immunotherapeutic Response of Bladder Cancer Patients. Int. J. Mol. Sci. 2022, 23, 15970. https://doi.org/10.3390/ijms232415970
Chen H, Yang W, Xue X, Li Y, Jin Z, Ji Z. Integrated Analysis Revealed an Inflammatory Cancer-Associated Fibroblast-Based Subtypes with Promising Implications in Predicting the Prognosis and Immunotherapeutic Response of Bladder Cancer Patients. International Journal of Molecular Sciences. 2022; 23(24):15970. https://doi.org/10.3390/ijms232415970
Chicago/Turabian StyleChen, Hualin, Wenjie Yang, Xiaoqiang Xue, Yingjie Li, Zhaoheng Jin, and Zhigang Ji. 2022. "Integrated Analysis Revealed an Inflammatory Cancer-Associated Fibroblast-Based Subtypes with Promising Implications in Predicting the Prognosis and Immunotherapeutic Response of Bladder Cancer Patients" International Journal of Molecular Sciences 23, no. 24: 15970. https://doi.org/10.3390/ijms232415970