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Updated: Feb 5, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Identification of Key Genes and Pathways in Triple-Negative Breast Cancer by Integrated Bioinformatics Analysis
Pengzhi Dong1, Bing Yu2, Lanlan Pan1
1Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Purpose:
Triple-negative breast cancer refers to breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2). This study aimed to identify the key pathways and genes and find the potential initiation and progression mechanism of triple-negative breast cancer (TNBC).
Methods:
We downloaded the gene expression profiles of GSE76275 from Gene Expression Omnibus (GEO) datasets. This microarray Super-Series sets are composed of gene expression data from 265 samples which included 67 non-TNBC and 198 TNBC. Next, all the differentially expressed genes (DEGs) with p<0.01 and fold change ≥1.5 or ≤-1.5 were identified.
Result:
56 upregulated and 151 downregulated genes were listed and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis was performed. These significantly changed genes were mainly involved in the biological process termed prostate gland morphogenesis, inner ear morphogenesis, cell maturation, digestive tract morphogenesis, autonomic nervous system development, monovalent inorganic anion homeostasis, neural crest cell development, regulation of dendrite extension and glial cell proliferation, immune system process termed T cell differentiation, regulation of immune response, and macrophage activation. Genes are mainly involved in the KEGG pathway termed Oocyte meiosis. All DEGs underwent survival analysis using datasets from The Cancer Genome Atlas (TCGA) integrated by cBioPortal, of which amplification of SRY-related HMG-box 8 (SOX8), androgen receptor (AR), and Chromosome 9 Open Reading Frame 152 (C9orf152) were significantly negative while Nik Related Kinase (NRK) and RAS oncogene family 30 (RAB30) were positively correlated to the life expectancy (p<0.05).
Conclusions:
In conclusion, these pathways and genes identified could help understanding the mechanism of development of TNBC. Besides, SOX8, AR, C9orf152, NRK and RAB30, and other key genes and pathways might be promising targets for the TNBC treatment.
Insights
Researchers identified key genes and pathways involved in triple-negative breast cancer (TNBC) development. Specific genes like SOX8 and AR were linked to patient survival, offering potential new TNBC treatment targets.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2).
- Understanding TNBC's initiation and progression mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To identify key pathways and genes implicated in TNBC.
- To elucidate the potential mechanisms driving TNBC initiation and progression.
Main Methods:
- Gene expression profiles from 265 samples (67 non-TNBC, 198 TNBC) were analyzed from the GSE76275 dataset.
- Differentially expressed genes (DEGs) were identified using stringent statistical criteria (p<0.01, fold change ≥1.5 or ≤-1.5).
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on DEGs.
Main Results:
- 56 genes were upregulated and 151 downregulated in TNBC.
- DEGs were significantly enriched in pathways related to morphogenesis, cell maturation, nervous system development, and immune processes like T cell differentiation and macrophage activation.
- Survival analysis revealed that amplification of SOX8, AR, and C9orf152 correlated with poorer outcomes, while NRK and RAB30 showed positive correlation with life expectancy.
Conclusions:
- The identified pathways and genes provide insights into TNBC development mechanisms.
- SOX8, AR, C9orf152, NRK, and RAB30 represent potential therapeutic targets for TNBC treatment.
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