Transcriptional Alterations in Triple-Negative Breast Cancer: Differential Expression, Functional Enrichment and Co-Expression Network Analysis of TCGA-BRCA

<title>Abstract</title> <p> Triple-negative breast cancer (TNBC) accounts for 10-15% of breast cancers and exhibits poor prognosis. While known to be biologically heterogeneous, the transcriptional architecture distinguishing normal-to-TNBC transition from intrinsic tumor heterogeneity remains unclear. I analyzed 115 TNBC and 113 normal samples from TCGA-BRCA using differential expression, Gene Ontology enrichment, and co-expression network analysis. I identified 3,016 dysregulated genes (padj &lt; 0.05, |log2FC| ≥ 2): upregulated mitotic genes ( <italic>TPX2, CDCA8, AURKA</italic> ) and downregulated structural genes ( <italic>PDE2A, CAVIN2, ABCA9</italic> ). Notably, all top 50 hub genes in the combined TNBC + Normal network were uniformly downregulated, contrasting with distinct hubs in the TNBC-specific network. This asymmetry suggests TNBC involves coordinated loss of normal tissue architecture, distinct from intrinsic tumor heterogeneity. Cox regression revealed no significant association between hub genes and survival. </p>