Model-Based Integration Analysis Revealed Presence of Novel Prognostic miRNA Targets and Important Cancer Driver Genes in Triple-Negative Breast Cancers
Abstract
:1. Introduction
2. Results
2.1. miRNAs Differentially Expressed among the Tumour Subtypes
2.2. miRNAs Associated with Survival
2.3. In silico Validation
2.4. mRNA Differentially Expressed among the Tumour Subtype Classes
2.5. Prognostic miRNAs and Their Association with Predicted Targets and Enriched Functions
2.6. 18.-miRNAs Signature
2.7. 10.-miRNAs Signature
3. Discussion
4. Material and Methods
4.1. Data and Pre-Processing
4.2. Collection of Predicted, Validated Targets and Calculation of Correlation Index
4.3. Statistical Analysis
4.4. Gene Set Enrichment Analysis of Predicted Targets
4.5. Independent Cohorts for Validation for miRNA Prognostic Signature
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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miRNAs | HR | Lower | Higher | p-Value | TNBC vs Non-TNBC | ||
---|---|---|---|---|---|---|---|
Regulation | p-Value | Type | |||||
hsa-miR-29c | 0.72 | 0.52 | 1 | 0.0469 | Up | 1.73E-16 | Protective |
hsa-miR-342-3p | 0.52 | 0.31 | 0.89 | 0.0162 | Up | 2.99E-12 | Protective |
hsa-miR-342-5p | 0.3 | 0.1 | 0.93 | 0.0356 | Up | 1.49E-09 | Protective |
hsa-let-7c | 0.63 | 0.41 | 0.98 | 0.0411 | Up | 4.25E-06 | Protective |
hsa-miR-19b-1 * | 0 | 0 | 0.69 | 0.0374 | Down | 9.29E-06 | Protective |
hsa-let-7b | 0.5 | 0.31 | 0.83 | 0.0057 | Up | 9.60E-06 | Protective |
hsa-miR-1290 | 1.71 | 1.2 | 2.43 | 0.0022 | Down | 2.61E-04 | Risky |
hsa-miR-369-5p | 0 | 0 | 0.42 | 0.0262 | Up | 5.27E-04 | Protective |
hsa-miR-301b | 5.31 | 1.13 | 24.96 | 0.0324 | Down | 6.60E-04 | Risky |
hsa-miR-630 | 1.64 | 1.17 | 2.3 | 0.0029 | Down | 2.26E-03 | Risky |
hsa-miR-101 | 0.58 | 0.33 | 1 | 0.0486 | Up | 7.98E-03 | Protective |
hsa-miR-1246 | 1.53 | 1.12 | 2.09 | 0.0071 | Down | 1.03E-02 | Risky |
hsa-miR-181d | 0.31 | 0.1 | 0.95 | 0.0382 | Down | 1.13E-02 | Protective |
hsa-miR-181c * | 0.1 | 0.01 | 0.76 | 0.0244 | Down | 1.39E-02 | Protective |
hsa-miR-30e | 0.49 | 0.25 | 0.98 | 0.0436 | Down | 1.63E-02 | Protective |
hsa-miR-497 | 0.51 | 0.29 | 0.9 | 0.0193 | Up | 2.30E-02 | Protective |
hsa-miR-154 | 0.05 | 0 | 0.58 | 0.0168 | Up | 3.28E-02 | Protective |
hsa-miR-130a | 0.5 | 0.33 | 0.78 | 0.0017 | Down | 4.22E-02 | Protective |
miRNA | HR | Lower | Higher | p-Value | TNBC vs Non-TNBC | ||
---|---|---|---|---|---|---|---|
Regulation | P-Value | Type | |||||
hsa-miR-342-3p | 0.68 | 0.5 | 0.92 | 0.0127 | Up | 2.99E-12 | Protective |
hsa-miR-342-5p | 0.39 | 0.2 | 0.75 | 0.00415 | Up | 1.49E-09 | Protective |
hsa-miR-193b | 1.5 | 1 | 2.25 | 0.0487 | Up | 3.23E-09 | Risky |
hsa-miR-195 | 0.76 | 0.59 | 0.98 | 0.0325 | Up | 1.56E-03 | Protective |
hsa-miR-155 | 0.61 | 0.41 | 0.91 | 0.0157 | Down | 7.44E-03 | Protective |
hsa-miR-936 | 5.79 | 1.04 | 32.08 | 0.0442 | Up | 1.17E-02 | Protective |
hsa-miR-338-3p | 0.43 | 0.19 | 0.96 | 0.0377 | Up | 1.40E-02 | Protective |
hsa-miR-1208 | 376.22 | 10.32 | 13709.16 | 0.00111 | Down | 1.78E-02 | Risky |
hsa-miR-497 | 0.64 | 0.44 | 0.94 | 0.021 | Up | 2.30E-02 | Protective |
hsa-miR-146b-5p | 0.65 | 0.45 | 0.94 | 0.0212 | Down | 2.39E-02 | Protective |
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Zaka, M.; Sutton, C.W.; Peng, Y.; Konur, S. Model-Based Integration Analysis Revealed Presence of Novel Prognostic miRNA Targets and Important Cancer Driver Genes in Triple-Negative Breast Cancers. Cancers 2020, 12, 632. https://doi.org/10.3390/cancers12030632
Zaka M, Sutton CW, Peng Y, Konur S. Model-Based Integration Analysis Revealed Presence of Novel Prognostic miRNA Targets and Important Cancer Driver Genes in Triple-Negative Breast Cancers. Cancers. 2020; 12(3):632. https://doi.org/10.3390/cancers12030632
Chicago/Turabian StyleZaka, Masood, Chris W. Sutton, Yonghong Peng, and Savas Konur. 2020. "Model-Based Integration Analysis Revealed Presence of Novel Prognostic miRNA Targets and Important Cancer Driver Genes in Triple-Negative Breast Cancers" Cancers 12, no. 3: 632. https://doi.org/10.3390/cancers12030632