Machine learning-guided differential gene expression analysis identifies a highly-connected seven-gene cluster in triple-negative breast cancer.

Background: One of the most challenging cancers is triple-negative breast cancer, which is subdivided into many molecular subtypes. Due to the high degree of heterogeneity, the role of precision medicine remains challenging. With the use of machine learning (ML)-guided gene selection, the differential gene expression analysis can be optimized, and eventually, the process of precision medicine can see great advancement through biomarker discovery. Purpose: Enhancing precision medicine in the oncology field by identification of the most representative differentially-expressed genes to be used as biomarkers or as novel drug targets. Methods: By utilizing data from the Gene Expression Omnibus (GEO) repository and The Cancer Genome Atlas (TCGA), we identified the differentially expressed genes using the linear model for microarray analysis (LIMMA) and edgeR algorithms, and applied ML-based feature selection using several algorithms. Results: A total of 27 genes were selected by merging features identified with both LIMMA and ML-based feature selection methods. The models with the highest area under the curve (AUC) are CatBoost, Extreme Gradient Boosting (XGBoost), Random Forest, and Multi-Layer Perceptron classifiers. ESR1, FOXA1, GATA3, XBP1, GREB1, AR, and AGR2 were identified as hub genes in a highly interconnected cluster. Conclusion: ML-based gene selection shows a great impact on the identification of hub genes. The ML models built can improve precision oncology in diagnosis and prognosis. The identified hub genes can serve as biomarkers and warrant further research for potential drug target development.