Metabolic Rewiring in Triple-Negative Breast Cancer: Systems Analysis of TCGA-BRCA Transcriptome Reveals Prognostic Hub Genes
Chandrasekar, S.
Show abstract
Triple Negative Breast Cancer (TNBC) is the deadliest and most aggressive subtype of breast cancer, with poor prognosis and high rates of metastasis. Despite knowledge of metabolic rewiring in TNBC, the systems-level coordination of these adaptive pathways remains unmapped. This integrative systems-level analysis reveals key metabolic hub genes and identifies ATP1A2 as a significant prognostic marker. Analysis identified 764 differentially expressed genes, with 89 enriched biological processes predominantly involving metabolic pathways. Co-expression network analysis of 261 genes identified metabolic hub genes including LEP, ADIPOQ, and ATP1A2. To evaluate the prognostic framework, survival analysis of the top 10 hubs was performed on synthetic survival data, revealing ATP1A2 as a significant marker (p = 0.03) under Cox regression, with elevated expression associating with altered survival outcomes. By systematically mapping metabolic rewiring in TNBC, this work identifies ATP1A2 as an actionable therapeutic target and establishes a systems-level framework for rational drug discovery and patient stratification in this aggressive malignancy.
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