Identification of Alternatively-Activated Pathways between Primary Breast Cancer and Liver Metastatic Cancer Using Microarray Data
Abstract
:1. Introduction
2. Materials and Methods
2.1. Gene Expression and Pathways
2.2. Gene Expression Data Pretreatment
2.3. Breast Cancer Liver Metastasis Uniquely-Enriched Pathway Analysis
2.4. Gene-Gene Activity Alteration Patterns’ Recognition
2.5. Bayesian Network Construction
2.6. Expand Pathways with the Bayesian Network
2.7. Connectivity among Pathways: Pathway Networks
3. Results
3.1. Raw Pathway Analysis
3.2. Robustness Analysis
3.3. Expanded Network
3.4. Pathway Network
3.5. Alternatively-Activated Pathways
4. Discussions
5. Conclusions
Availability of Data and Materials
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Pathway Resource | Number of Significant Primary Cancer-Related Pathways | Number of Significant Metastatic Cancer-Related Pathways |
---|---|---|
Raw pathways | 17 | 24 |
Expanded pathways by primary cancer Bayesian network 1 time | 22 | 13 |
Expanded pathways by primary cancer Bayesian network 2 times | 41 | 0 |
Expanded pathways by primary cancer Bayesian network 3 time | 55 | 0 |
Expanded pathways by metastatic cancer Bayesian network 1 time | 11 | 34 |
Expanded pathways by metastatic cancer Bayesian network 2 times | 5 | 49 |
Expanded pathways by metastatic cancer Bayesian network 3 time | 1 | 48 |
Type | Cytokine | Cytokine Receptor | Pattern | Function |
---|---|---|---|---|
Chemokines | CXCL11 | CXCR3 | 10→01 | CXCR3 is a molecular target in breast cancer metastasis [48,49] |
CXCL13 | BLR1 | 10→01 | CXCL13 is overexpressed in breast cancer patients [50,51] | |
CCL2 | CCR2 | 10→01 | the CCL2-triggered chemokine cascade in macrophages promotes metastatic seeding of breast cancer cells, thereby amplifying the pathology already extant in the system [52] CCL2/CCR2 chemokine signaling coordinates the survival and motility of breast cancer cells with implications on the metastatic process [53] | |
PDG family | VEGFC | FLT4 | 10→01 | activation of the VEGF-C/Flt-4 axis enhances mobility of cancer cells and contributes to the promotion of metastasis in animals [54] VEGF-C-VEGFR3/Flt4 axis regulates mammary tumor growth and metastasis in an autocrine manner [55] VEGF-C/D and Flt-4 may play an important role in the process of lymphatic metastasis of early-stage invasive cervical carcinoma through paracrine and autocrine mechanisms [56] |
FLT3LG | FLT3 | 10→01 | FLT3-ligand administration inhibits liver metastases [57] | |
TNF family | TNFSF8 | TNFRSF8 | 10→01 | TNF inhibitor suppresses bone metastasis in a breast cancer cell line [58] |
IL-1 family | IL1B | IL1R2 | 10→01 | IL-1B is a potential biomarker for predicting breast cancer patients at increased risk for developing bone metastasis [59] IL-1 drives breast cancer growth and bone metastasis in vivo [60] |
IL-10 family | IL20 | IL20RA | 01→10 | IL-20 plays pivotal roles in the tumor progression of breast cancer; IL-20 may be a novel target in treating breast tumor-induced osteolysis [61] |
IL22 | IL22RA2 | 01→10 | IL-22 promotes epithelial cell transformation and breast tumorigenesis [62] | |
TGF-b family | BMP2 | BMPR1B | 01→10 | Bone morphogenic proteins are related to driving breast cancer metastasis to bone [63] The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases’ formation [64] TGF-β activity is controlled by the expression of BMP7; BMP7 expression has been shown to be inversely proportional to the tumorigenicity and invasive behavior of MDA-MB-231 breast cancer cells [65] The presence of high levels of BMP7 expression in primary tumors has been strongly associated with accelerated bone metastasis, especially from ductal carcinomas [66] |
BMP7 | ||||
Hematopoietic | IL12A | IL12RB1 | 10→01 | NA |
IL12B | 10→01 |
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Wang, L.; Li, J.; Liu, E.; Kinnebrew, G.; Zhang, X.; Stover, D.; Huo, Y.; Zeng, Z.; Jiang, W.; Cheng, L.; et al. Identification of Alternatively-Activated Pathways between Primary Breast Cancer and Liver Metastatic Cancer Using Microarray Data. Genes 2019, 10, 753. https://doi.org/10.3390/genes10100753
Wang L, Li J, Liu E, Kinnebrew G, Zhang X, Stover D, Huo Y, Zeng Z, Jiang W, Cheng L, et al. Identification of Alternatively-Activated Pathways between Primary Breast Cancer and Liver Metastatic Cancer Using Microarray Data. Genes. 2019; 10(10):753. https://doi.org/10.3390/genes10100753
Chicago/Turabian StyleWang, Limei, Jin Li, Enze Liu, Garrett Kinnebrew, Xiaoli Zhang, Daniel Stover, Yang Huo, Zhi Zeng, Wanli Jiang, Lijun Cheng, and et al. 2019. "Identification of Alternatively-Activated Pathways between Primary Breast Cancer and Liver Metastatic Cancer Using Microarray Data" Genes 10, no. 10: 753. https://doi.org/10.3390/genes10100753