Systems Medicine Design for Triple-Negative Breast Cancer and Non-Triple-Negative Breast Cancer Based on Systems Identification and Carcinogenic Mechanisms
Abstract
:1. Introduction
2. Results
2.1. Distinctive Core Signaling Pathways for TNBC
2.2. Distinctive Core Signaling Pathways for Non-TNBC
2.3. Common Core Signaling Pathways of TNBC and Non-TNBC
3. Discussion
3.1. The Carcinogenic Molecular Mechanisms in TNBC
3.2. The Carcinogenic Molecular Mechanisms in Non-TNBC
3.3. The Common Carcinogenic Molecular Mechanisms between TNBC and Non-TNBC
3.4. Exploring Multi-Molecule Drugs for TNBC and Non-TNBC Based on Drug Regulation Ability and Toxicity
4. Materials and Methods
4.1. Overview of the Systems Medicine Design Procedure
4.2. Construction Candidate Genome-Wide Genetic and Epigenetic Network (GWGEN) by Microarray Data of TNBC and Non-TNBC
4.3. Systems Modeling for Candidate Genome-Wide Genetic and Epigenetic Network (GWGEN)
4.4. Systems Identification and Systems Model Order Selection for Obtaining Real GWGEN of TNBC and Non-TNBC
4.5. Principal Network Projection (PNP) Method to Extract Core GWGENs of TNBC and Non-TNBC from Their Corresponding Real GWGENs
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nodes/Edges | Candidate GWGEN | Real TNBC GWGEN | Real Non-TNBC GWGEN |
---|---|---|---|
TF-lncRNA | 375 | 271 | 276 |
TF-miRNA | 526 | 500 | 503 |
TF-protein | 85,782 | 80,065 | 79,471 |
TF-TF | 32,600 | 26,025 | 25,514 |
TFs | 2567 | 2033 | 2108 |
lncRNA-lncRNA | 6 | 5 | 5 |
lncRNA-miRNA | 0 | 0 | 0 |
lncRNA-protein | 1036 | 590 | 717 |
lncRNA-TF | 420 | 184 | 220 |
lncRNAs | 425 | 313 | 238 |
miRNA-lncRNA | 88 | 61 | 64 |
miRNA-miRNA | 1 | 1 | 1 |
miRNA-protein | 31,020 | 20,206 | 20,861 |
miRNA-TF | 6708 | 3747 | 3551 |
miRNAs | 205 | 143 | 143 |
Receptors | 2377 | 2207 | 2211 |
PPIs | 4,639,077 | 2,478,528 | 1,967,333 |
Proteins | 15,361 | 14,993 | 15,282 |
Total nodes | 20,355 | 19,689 | 19,982 |
Total edges | 4,797,639 | 2,610,183 | 2,098,516 |
Pathway Analysis | Numbers | p-Value |
---|---|---|
Pathways in cancer | 121 | 1.47 |
PI3K-Akt signaling pathway | 102 | 5.30 |
MicroRNAs in cancer | 81 | 9.38 |
MAPK signaling pathway | 80 | 1.15 |
Transcriptional misregulation in cancer | 77 | 2.24 |
Pathway Analysis | Numbers | p-Value |
---|---|---|
Pathways in cancer | 108 | 3.27 |
PI3K-Akt signaling pathway | 104 | 1.60 |
MicroRNAs in cancer | 85 | 3.02 |
Transcriptional misregulation in cancer | 77 | 5.18 |
T cell receptor signaling pathway | 53 | 3.80 |
Drugs | BRCA1 | AKT1 | FOXC1 | MMP2 | ETS1 | STAT3 | |
---|---|---|---|---|---|---|---|
Targets | |||||||
Resveratrol | ● | ● | ● | ● | |||
Sirolimus | ● | ||||||
Prednisolone | ● | ● | ● | ● |
Drugs | BRCA1 | AKT1 | FOXC1 | MMP2 | NFE2L1 | |
---|---|---|---|---|---|---|
Targets | ||||||
Resveratrol | ● | ● | ● | |||
Sirolimus | ● | |||||
Carbamazepine | ● | ● | ||||
Verapamil | ● | ● |
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Yeh, S.-J.; Hsu, B.-J.; Chen, B.-S. Systems Medicine Design for Triple-Negative Breast Cancer and Non-Triple-Negative Breast Cancer Based on Systems Identification and Carcinogenic Mechanisms. Int. J. Mol. Sci. 2021, 22, 3083. https://doi.org/10.3390/ijms22063083
Yeh S-J, Hsu B-J, Chen B-S. Systems Medicine Design for Triple-Negative Breast Cancer and Non-Triple-Negative Breast Cancer Based on Systems Identification and Carcinogenic Mechanisms. International Journal of Molecular Sciences. 2021; 22(6):3083. https://doi.org/10.3390/ijms22063083
Chicago/Turabian StyleYeh, Shan-Ju, Bo-Jie Hsu, and Bor-Sen Chen. 2021. "Systems Medicine Design for Triple-Negative Breast Cancer and Non-Triple-Negative Breast Cancer Based on Systems Identification and Carcinogenic Mechanisms" International Journal of Molecular Sciences 22, no. 6: 3083. https://doi.org/10.3390/ijms22063083