Enhanced Thermogenesis in Triple-Negative Breast Cancer Is Associated with Pro-Tumor Immune Microenvironment
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Breast Cancer Cohorts
2.2. Gene Set Enrichment Analysis (GSEA)
2.3. Analyses of Infiltrating Immune Cells Using xCell Algorithm
2.4. Signaling Signature
2.5. Statistical Analysis
3. Results
3.1. High Thermogenesis Score Is Associated with a Trend towards Worse Survival in Triple-Negative Breast Cancer (TNBC)
3.2. Thermogenesis Is Lower in TNBC, and Low-Thermogenesis TNBC Is Associated with Higher Nottingham Histological Grade and Higher MKi67 Expression
3.3. High-Thermogenesis TNBC Is Associated with Elevated Intratumoral Adipocytes and the Expression of Mature Vascular-Related Genes, but Not with Mutation Rates
3.4. Thermogenesis Is Associated with a Trend towards Higher Response to Neoadjuvant Chemotherapy (NAC)
3.5. High-Thermogenesis TNBC Enriched Fatty Acid Metabolism and Adipogenesis Pathways while Low-Thermogenesis TNBC Enriched Cell-Proliferation-Related and Immune-Related Pathways
3.6. Low-Thermogenesis TNBC Is Associated with Higher Cytolytic T-cell (CTL)-Attracting Chemokines, whereas High-Thermogenesis TNBC Is Associated with Higher Myeloid-Derived Suppressor Cell (MDSC)-/Regulatory T-cells (Tregs)-Attracting Chemokines, with Glucocorticoid Receptor (GR) Signaling
3.7. High-Thermogenesis TNBC Has Lower Anti-Cancer Immune Cell Infiltration, Lower Cytolytic Activity, and Higher M2 Macrophages
4. Discussion
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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Gandhi, S.; Oshi, M.; Murthy, V.; Repasky, E.A.; Takabe, K. Enhanced Thermogenesis in Triple-Negative Breast Cancer Is Associated with Pro-Tumor Immune Microenvironment. Cancers 2021, 13, 2559. https://doi.org/10.3390/cancers13112559
Gandhi S, Oshi M, Murthy V, Repasky EA, Takabe K. Enhanced Thermogenesis in Triple-Negative Breast Cancer Is Associated with Pro-Tumor Immune Microenvironment. Cancers. 2021; 13(11):2559. https://doi.org/10.3390/cancers13112559
Chicago/Turabian StyleGandhi, Shipra, Masanori Oshi, Vijayashree Murthy, Elizabeth A. Repasky, and Kazuaki Takabe. 2021. "Enhanced Thermogenesis in Triple-Negative Breast Cancer Is Associated with Pro-Tumor Immune Microenvironment" Cancers 13, no. 11: 2559. https://doi.org/10.3390/cancers13112559