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Updated: Feb 4, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Integrated network analysis and machine learning approach for the identification of key genes of triple-negative
Leimarembi Devi Naorem1, Mathavan Muthaiyan1, Amouda Venkatesan1
1Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry, India.
Abstract:
Triple-negative breast cancer (TNBC) has attracted more attention compared with other breast cancer subtypes due to its aggressive nature, poor prognosis, and chemotherapy remains the mainstay of treatment with no other approved targeted therapy. Therefore, the study aimed to discover more promising therapeutic targets and investigating new insights of biological mechanism of TNBC. Six microarray data sets consisting of 463 non-TNBC and 405 TNBC samples were mined from Gene Expression Omnibus. The data sets were integrated by meta-analysis and identified 1075 differentially expressed genes. Protein-protein interaction network was constructed which consists of 486 nodes and 1932 edges, where 29 hub genes were obtained with high topological measures. Further, 16 features (hub genes), 12 upregulated (AURKB, CCNB2, CDC20, DDX18, EGFR, ENO1, MYC, NUP88, PLK1, PML, POLR2F, and SKP2) and four downregulated ( CCND1, GLI3, SKP1, and TGFB3) were selected through machine learning correlation based feature selection method on training data set. A naïve Bayes based classifier built using the expression profiles of 16 features (hub genes) accurately and reliably classify TNBC from non-TNBC samples in the validation test data set with a receiver operating curve of 0.93 to 0.98. Subsequently, Gene Ontology analysis revealed that the hub genes were enriched in mitotic cell cycle processes and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that they were enriched in cell cycle pathways. Thus, the identified key hub genes and pathways highlighted in the study would enhance the understanding of molecular mechanism of TNBC which may serve as potential therapeutic target.
Insights
Researchers identified key genes and cell cycle pathways in triple-negative breast cancer (TNBC). This discovery offers potential new therapeutic targets for this aggressive cancer subtype, improving treatment options.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Triple-negative breast cancer (TNBC) is aggressive with poor prognosis, lacking targeted therapies beyond chemotherapy.
- Identifying novel therapeutic targets and understanding TNBC's biological mechanisms are critical.
Purpose of the Study:
- To discover promising therapeutic targets for TNBC.
- To investigate new insights into the biological mechanisms of TNBC.
Main Methods:
- Integrated six microarray datasets (463 non-TNBC, 405 TNBC) using meta-analysis.
- Constructed a protein-protein interaction network to identify 29 hub genes.
- Utilized machine learning for feature selection, identifying 16 key hub genes (12 upregulated, 4 downregulated).
- Developed a Naïve Bayes classifier to distinguish TNBC from non-TNBC samples.
Main Results:
- Identified 1075 differentially expressed genes and 29 hub genes.
- Selected 16 significant hub genes, including upregulated AURKB, CCNB2, CDC20, and downregulated CCND1, GLI3.
- Achieved high classification accuracy (ROC 0.93-0.98) for TNBC detection using the 16-gene classifier.
- Gene Ontology and KEGG pathway analyses revealed enrichment in mitotic and cell cycle processes.
Conclusions:
- The identified hub genes and cell cycle pathways provide a deeper understanding of TNBC's molecular mechanisms.
- These findings highlight potential novel therapeutic targets for TNBC treatment.
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