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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Molecular Features of Triple Negative Breast Cancer: Microarray Evidence and Further Integrated Analysis
Jinsong He1, Jianbo Yang2, Weicai Chen1
1Department of Breast Surgery, The first affiliated hospital of Shenzhen university, the Second People's Hospital of Shenzhen, Shenzhen 518035, China.
Purpose:
Breast cancer is a heterogeneous disease usually including four molecular subtypes such as luminal A, luminal B, HER2-enriched, and triple-negative breast cancer (TNBC). TNBC is more aggressive than other breast cancer subtypes. Despite major advances in ER-positive or HER2-amplified breast cancer, there is no targeted agent currently available for TNBC, so it is urgent to identify new potential therapeutic targets for TNBC.
Methods:
We first used microarray analysis to compare gene expression profiling between TNBC and non-TNBC. Furthermore an integrated analysis was conducted based on our own and published data, leading to more robust, reproducible and accurate predictions. Additionally, we performed qRT-PCR in breast cancer cell lines to verify the findings in integrated analysis.
Results:
After searching Gene Expression Omnibus database (GEO), two microarray studies were obtained according to the inclusion criteria. The integrated analysis was conducted, including 30 samples of TNBC and 77 samples of non-TNBC. 556 genes were found to be consistently differentially expressed (344 up-regulated genes and 212 down-regulated genes in TNBC). Functional annotation for these differentially expressed genes (DEGs) showed that the most significantly enriched Gene Ontology (GO) term for molecular functions was protein binding (GO: 0005515, P = 6.09E-21), while that for biological processes was signal transduction (GO: 0007165, P = 9.46E-08), and that for cellular component was cytoplasm (GO: 0005737, P = 2.09E-21). The most significant pathway was Pathways in cancer (P = 6.54E-05) based on Kyoto Encyclopedia of Genes and Genomes (KEGG). DUSP1 (Degree = 21), MYEOV2 (Degree = 15) and UQCRQ (Degree = 14) were identified as the significant hub proteins in the protein-protein interaction (PPI) network. Five genes were selected to perform qRT-PCR in seven breast cancer cell lines, and qRT-PCR results showed that the expression pattern of selected genes in TNBC lines and non-TNBC lines was nearly consistent with that in the integrated analysis.
Conclusion:
This study may help to understand the pathogenesis of different breast cancer subtypes, contributing to the successful identification of therapeutic targets for TNBC.
Insights
This study identifies 556 differentially expressed genes in triple-negative breast cancer (TNBC), including key hub proteins, offering potential therapeutic targets for this aggressive cancer subtype.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Breast cancer comprises diverse molecular subtypes, with triple-negative breast cancer (TNBC) exhibiting higher aggressiveness.
- Current treatments for ER-positive or HER2-amplified breast cancer are advanced, yet TNBC lacks targeted therapies, necessitating urgent identification of new therapeutic targets.
Purpose of the Study:
- To identify novel therapeutic targets for triple-negative breast cancer (TNBC) by analyzing gene expression profiles.
- To understand the molecular pathogenesis underlying TNBC compared to other breast cancer subtypes.
Main Methods:
- Gene expression profiling using microarray analysis comparing TNBC and non-TNBC samples.
- Integrated analysis of own and published data for robust gene expression comparisons.
- Quantitative reverse transcription PCR (qRT-PCR) to validate findings in breast cancer cell lines.
Main Results:
- Integrated analysis of 30 TNBC and 77 non-TNBC samples revealed 556 consistently differentially expressed genes.
- Functional annotation highlighted protein binding, signal transduction, and cytoplasm as significantly enriched terms.
- Key hub proteins DUSP1, MYEOV2, and UQCRQ were identified in the protein-protein interaction network.
- Expression patterns of selected genes were validated via qRT-PCR in TNBC and non-TNBC cell lines.
Conclusions:
- The identified differentially expressed genes and hub proteins provide insights into TNBC pathogenesis.
- This research contributes to the discovery of potential therapeutic targets for triple-negative breast cancer.

