A Novel Prognostic Signature of Mitophagy-Related E3 Ubiquitin Ligases in Breast Cancer
Abstract
1. Introduction
2. Results
2.1. Construction of Mitophagy-Related E3 Ubiquitin Ligase Prognostic Model
2.2. ASUW Prognostic Model Effectively Predicted Poor Breast Cancer Outcomes
2.3. Functional Enrichment Analyses of DEGs Between Two Groups
2.4. TIME Comparisons Between Two Groups Under ASUW Prognostic Model
2.5. Prediction of Sensitive Drugs for BRCA Under ASUW Prognostic Model
2.6. Analyses of mtDNA Stress, SASP, and VDIM for Two Groups Under ASUW Prognostic Model
3. Discussion
4. Materials and Methods
4.1. Data Collection and Preparation of BRCA
4.2. Mitophagy-Related Gene Collection
4.3. Univariate Cox Regression Analysis
4.4. Construction of a Prognostic Model
4.5. Overall Survival Analysis
4.6. DEG Identification
4.7. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Analyses
4.8. Gene Set Enrichment Analysis (GSEA)
4.9. ESTIMATE Analysis
4.10. Evaluation of Drug Sensitivity
4.11. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
SASP | Senescence-associated secretory phenotype |
TME | Tumor microenvironment |
BRCA | Breast cancer |
TIME | Tumor immune microenvironment |
TCGA | The Cancer Genome Atlas |
GEO | Gene Expression Omnibus |
OS | Overall survival |
VDIMs | Vesicles derived from the inner mitochondrial membrane |
GSEA | Gene set enrichment analysis |
LASSO | Least absolute shrinkage and selector operator |
ROC | Receiver operating characteristic |
AUC | Area under the curve |
DEG | Differentially expressed gene |
GO | Gene ontology |
BP | Biological processes |
CC | Cellular component |
MF | Molecular function |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
GSEA | Gene set enrichment analysis |
MSigDB | Molecular Signatures Database |
HR | Hazard ratio |
CI | Confidence interval |
KM | Kaplan–Meier |
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Gene Symbol | Gene ID | Full Name | Classes | Risk Coefficient |
---|---|---|---|---|
ARIH1 | 25820 | Ariadne RBR E3 Ubiquitin Protein Ligase 1 | RING-IBR-RING (RBR) | −0.100073572 |
SIAH2 | 6478 | Siah E3 Ubiquitin Protein Ligase 2 | Really interesting new gene (RING) | −0.333969422 |
UBR5 | 51366 | Ubiquitin Protein Ligase E3 Component N-Recognin 5 | Homologous to the E6AP carboxyl terminus (HECT) | 0.34620336 |
WWP2 | 11060 | WW Domain Containing E3 Ubiquitin Protein Ligase 2 | Homologous to the E6AP carboxyl terminus (HECT) | −0.204703988 |
Characteristics | HR (95% CI) | p Value |
---|---|---|
Stage (vs. Stage I) | ||
Stage II | 1.21 [0.51, 2.83] | 0.666 |
Stage III | 1.81 [0.58, 5.66] | 0.304 |
Stage IV | 9.43 [0.76, 117.34] | 0.081 |
Tumor (vs. T1) | ||
T2 | 1.22 [0.65, 2.27] | 0.538 |
T3 | 1.18 [0.53, 2.62] | 0.678 |
T4 | 1.61 [0.65, 4.00] | 0.306 |
Lymph Node (vs. N0) | ||
N1 | 1.53 [0.94, 2.50] | 0.090 |
N2 | 1.71 [0.75, 3.90] | 0.206 |
N3 | 1.67 [0.74, 3.76] | 0.212 |
Metastasis (vs. M0) | ||
M1 | 0.71 [0.09, 5.95] | 0.756 |
Age | 1.03 [1.02, 1.05] | <0.001 |
Risk Score | 2.33 [1.67, 3.27] | <0.001 |
Drug Name | Target | Application | Reference | IC50 (High vs. Low) |
---|---|---|---|---|
MK-2206 | Akt | Lung cancer, breast cancer, Colorectal cancer | [41,42] | down |
Pictilisib | PI3K | Breast cancer, lung cancer | [43,44] | down |
Rapamycin | mTORC1 | Breast cancer, kidney cancer | [45,46] | down |
Sorafenib | VEGFR, PDGFR, RAF kinases | Hepatocellular carcinoma, gastric cancer | [47,48] | down |
BI-2536 | PLK1 | Breast cancer, lung cancer | [49,50] | up |
GSK1904529A | IGF-1R | Breast cancer | [51] | down |
Uprosertib | Akt | Colorectal cancer | [52] | down |
LGK974 | Porcupine | Colorectal cancer | [53] | down |
Elephantin | Unclear | Further investigation is required | Unclear | down |
AZD5363 | Akt | Breast cancer | [54] | down |
Ipatasertib | Akt | Breast cancer, prostate cancer | [55,56] | down |
AT13148 | AGC family kinases | Pancreatic ductal adenocarcinoma | [57] | down |
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Bian, K.; Yang, C.; Zhang, F.; Huang, L. A Novel Prognostic Signature of Mitophagy-Related E3 Ubiquitin Ligases in Breast Cancer. Int. J. Mol. Sci. 2025, 26, 1551. https://doi.org/10.3390/ijms26041551
Bian K, Yang C, Zhang F, Huang L. A Novel Prognostic Signature of Mitophagy-Related E3 Ubiquitin Ligases in Breast Cancer. International Journal of Molecular Sciences. 2025; 26(4):1551. https://doi.org/10.3390/ijms26041551
Chicago/Turabian StyleBian, Kangjing, Chihyu Yang, Feng Zhang, and Lei Huang. 2025. "A Novel Prognostic Signature of Mitophagy-Related E3 Ubiquitin Ligases in Breast Cancer" International Journal of Molecular Sciences 26, no. 4: 1551. https://doi.org/10.3390/ijms26041551
APA StyleBian, K., Yang, C., Zhang, F., & Huang, L. (2025). A Novel Prognostic Signature of Mitophagy-Related E3 Ubiquitin Ligases in Breast Cancer. International Journal of Molecular Sciences, 26(4), 1551. https://doi.org/10.3390/ijms26041551