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Improved insight into the molecular mechanisms of triple negative breast cancer (TNBC) is required to predict prognosis and develop a new therapeutic strategy for targeted genes. The aim of this study is to identify key genes which may affect the prognosis of TNBC patients by bioinformatic analysis. In our study, the RNA sequencing (RNA-seq) expression data of 116 breast cancer lacking ER, PR, and HER2 expression and 113 normal tissues were downloaded from The Cancer Genome Atlas (TCGA). We screened out 147 differentially co-expressed genes in TNBC compared to non-cancerous tissue samples by using weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were constructed, revealing that 147 genes were mainly enriched in nuclear division, chromosomal region, ATPase activity, and cell cycle signaling. After using Cytoscape software for protein-protein interaction (PPI) network analysis and LASSO feature selection, a total of fifteen key genes were identified. Among them, BUB1 and CENPF were significantly correlated with the overall survival rate (OS) difference of TNBC patients (p value < 0.05). In addition, BUB1, CCNA2, and PACC1 showed significant poor disease-free survival (DFS) in TNBC patients (p value < 0.05), and may serve as candidate biomarkers in TNBC diagnosis. Thus, our results collectively suggest that BUB1, CCNA2, and PACC1 genes could play important roles in the progression of TNBC and provide attractive therapeutic targets. [ABSTRACT FROM AUTHOR]