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Updated: Dec 17, 2025

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Perturbations of pathway co-expression network identify a core network in metastatic breast cancer
Claudia Cava1, Simone Pini2, Donatella Taramelli3
1Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Via F.Cervi 93, 20090, Segrate, Milan, Italy.
Abstract:
Metastases are the main cause of death in advanced breast cancer (BC) patients. Although chemotherapy and hormone therapy are current treatment strategies, drug resistance is frequent and still not completely understood. In this study, a bioinformatics analysis was performed on BC patients to explore the molecular mechanisms associated with BC metastasis. Microarray gene expression profiles of metastatic and non metastatic BC patients were downloaded from Gene Expression Omnibus (GEO) dataset. Raw data were normalized and merged using the Combat tool. Pathways enriched with differently expressed genes were identified and a pathway co-expression network was generated using Pearson's correlation. We identified from this network, which includes 17 pathways and 128 interactions, the pathways that most influence the network efficiency. Moreover, protein interaction network was investigated to identify hub genes of the pathway network. The prognostic role of the network was evaluated with a survival analysis using an independent dataset. In conclusion, the pathway co-expression network could contribute to understanding the mechanism and development of BC metastases.
Insights
This study used bioinformatics to analyze breast cancer (BC) metastasis, identifying key molecular pathways and hub genes. The findings offer insights into BC progression and potential therapeutic targets for drug resistance.
Area of Science:
- Oncology
- Bioinformatics
- Genomics
Background:
- Metastasis is the primary cause of mortality in advanced breast cancer (BC).
- Current treatments like chemotherapy and hormone therapy face challenges due to frequent and poorly understood drug resistance.
- Understanding the molecular mechanisms of BC metastasis is crucial for improving patient outcomes.
Purpose of the Study:
- To explore the molecular mechanisms underlying breast cancer metastasis using bioinformatics analysis.
- To identify key pathways and genes involved in BC metastasis and drug resistance.
- To construct and analyze a pathway co-expression network for BC metastasis.
Main Methods:
- Downloaded and analyzed microarray gene expression profiles from the Gene Expression Omnibus (GEO) dataset for metastatic and non-metastatic BC patients.
- Normalized and merged gene expression data using the Combat tool.
- Generated a pathway co-expression network and investigated protein-protein interaction networks to identify hub genes.
Main Results:
- Identified 17 pathways and 128 interactions within the pathway co-expression network.
- Determined pathways that significantly influence network efficiency.
- Identified hub genes within the protein interaction network, suggesting their importance in BC metastasis.
Conclusions:
- The developed pathway co-expression network provides a framework for understanding BC metastasis mechanisms.
- The identified pathways and hub genes may offer novel targets for therapeutic strategies against BC metastasis and drug resistance.
- Further validation of the network's prognostic role is supported by survival analysis.
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