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Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Cross-platform meta-analysis of multiple gene expression profiles identifies novel expression signatures in acquired
Young Seok Lee1, Seung Won Ryu1, Se Jong Bae1
1Department of Biochemistry, Konkuk University School of Medicine, Seoul 143‑701, Republic of Korea.
Abstract:
Anthracyclines are among the most effective and commonly used chemotherapeutic agents. However, the development of acquired anthracycline resistance is a major limitation to their clinical application. The aim of the present study was to identify differentially expressed genes (DEGs) and biological processes associated with the acquisition of anthracycline resistance in human breast cancer cells. We performed a meta-analysis of publically available microarray datasets containing data on stepwise-selected, anthracycline‑resistant breast cancer cell lines using the RankProd package in R. Additionally, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to analyze GO term enrichment and pathways, respectively. A protein-protein interaction (PPI) network was also generated using Cytoscape software. The meta-analysis yielded 413 DEGs related to anthracycline resistance in human breast cancer cells, and 374 of these were not involved in individual DEGs. GO analyses showed the 413 genes were enriched with terms such as 'response to steroid metabolic process', 'chemical stimulus', 'external stimulus', 'hormone stimulus', 'multicellular organismal process', and 'system development'. Pathway analysis revealed significant pathways including steroid hormone biosynthesis, cytokine-cytokine receptor interaction, drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, and arachidonic acid metabolism. The PPI network indicated that proteins encoded by TRIM29, VTN, CCNA1, and karyopherin α 5 (KPNA5) participated in a significant number of interactions. In conclusion, our meta-analysis provides a comprehensive view of gene expression patterns associated with acquired resistance to anthracycline in breast cancer cells, and constitutes the basis for additional functional studies.
Insights
This study identified 413 differentially expressed genes linked to anthracycline resistance in breast cancer. Key biological processes and pathways were uncovered, offering new insights into treatment limitations.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Anthracyclines are vital chemotherapy drugs for breast cancer.
- Acquired resistance to anthracyclines significantly limits their clinical effectiveness.
- Understanding the genetic basis of this resistance is crucial for improving treatment outcomes.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) associated with anthracycline resistance in human breast cancer cells.
- To elucidate the biological processes and molecular pathways involved in the development of this resistance.
- To provide a foundation for further research into overcoming anthracycline resistance.
Main Methods:
- A meta-analysis of public microarray datasets was conducted using RankProd in R.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for enrichment and pathway analyses.
- A protein-protein interaction (PPI) network was constructed using Cytoscape software.
Main Results:
- The meta-analysis identified 413 DEGs related to anthracycline resistance, with 374 novel findings.
- GO analysis revealed enrichment in terms like 'response to steroid metabolic process' and 'hormone stimulus'.
- Significant pathways included steroid hormone biosynthesis, drug metabolism (cytochrome P450), and cytokine-cytokine receptor interaction. TRIM29, VTN, CCNA1, and KPNA5 were key interacting proteins.
Conclusions:
- This meta-analysis offers a comprehensive overview of gene expression changes in anthracycline-resistant breast cancer.
- The identified genes and pathways provide potential targets for future therapeutic strategies.
- Further functional studies are warranted to validate these findings and explore clinical applications.

