In Silico Analysis Predicts Nuclear Factors NR2F6 and YAP1 as Mesenchymal Subtype-Specific Therapeutic Targets for Ovarian Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Gene Expression Profiles and Data Pre-Processing
2.2. Enrichment of Hallmark Gene Signatures
2.3. In Silico Enrichment of Immune and Stromal Cell Type Signatures
2.4. Complementary Single-Cell Analysis of Tumour Composition
2.5. Cell–Cell Communication Analysis Combined with Cytokine Activity Inference
2.6. Correlation of Ligand–Receptor Pair Expression with Cancer Hallmarks
2.7. Inference of Transcription Factor Activity from Gene Expression Data
2.8. Inferred Transcription Factor Activity-Guided Intercellular Communication Network
2.9. Generation of a Prior Knowledge Network
2.10. Contextualization of Signalling Networks via Causal Reasoning
3. Results
3.1. Classification and Characterization of High-Grade Serous Ovarian Cancer Datasets
3.2. Compositional Analysis of High-Grade Serous Ovarian Cancer Subtypes Reveals Distinct Cell Type Proportions
3.3. Cell–Cell Interactions Drive Cancer Hallmarks in High-Grade Serous Ovarian Cancer
3.4. IL1B, TGFB1 and TNF Are Key Drivers of the Cancer Hallmarks in the MES Subtype
3.5. Intercellular Signalling Mediates Dysregulation of Transcription Factor Activity and Aberrant Cytokine Production in MES
3.6. Causal Inference Analysis Reveals YAP1 and NR2F6 as Novel Therapeutic Targets
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Kassuhn, W.; Cutillas, P.R.; Kessler, M.; Sehouli, J.; Braicu, E.I.; Blüthgen, N.; Kulbe, H. In Silico Analysis Predicts Nuclear Factors NR2F6 and YAP1 as Mesenchymal Subtype-Specific Therapeutic Targets for Ovarian Cancer Patients. Cancers 2023, 15, 3155. https://doi.org/10.3390/cancers15123155
Kassuhn W, Cutillas PR, Kessler M, Sehouli J, Braicu EI, Blüthgen N, Kulbe H. In Silico Analysis Predicts Nuclear Factors NR2F6 and YAP1 as Mesenchymal Subtype-Specific Therapeutic Targets for Ovarian Cancer Patients. Cancers. 2023; 15(12):3155. https://doi.org/10.3390/cancers15123155
Chicago/Turabian StyleKassuhn, Wanja, Pedro R. Cutillas, Mirjana Kessler, Jalid Sehouli, Elena I. Braicu, Nils Blüthgen, and Hagen Kulbe. 2023. "In Silico Analysis Predicts Nuclear Factors NR2F6 and YAP1 as Mesenchymal Subtype-Specific Therapeutic Targets for Ovarian Cancer Patients" Cancers 15, no. 12: 3155. https://doi.org/10.3390/cancers15123155