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This analysis examined GSE124647, a metastatic breast cancer gene expression dataset comprising 140 patients profiled on Affymetrix Human Genome U133 Plus 2.0 arrays (22,283 probesets). Patients were stratified into good survival (OS > 24.05 months or censored, n=88) versus poor survival (OS ≤ 24.05 months with death event, n=52) groups . The comprehensive workflow included differential expression analysis, pathway enrichment, and molecular subtyping to identify survival-associated signatures and therapeutic vulnerabilities.
The differential expression analysis identified 70 genes significantly associated with overall survival (FDR < 0.05), with a notable asymmetric regulation pattern: 41 genes downregulated and 29 genes upregulated in poor survival.
Expression patterns for the top 6 genes demonstrate robust separation between survival groups with gene symbols now clearly identifying each biomarker
IL6ST (Interleukin 6 Signal Transducer) emerges as the most robust biomarker, with 4 independent probesets (212196_at, 212195_at, 204864_s_at, 203685_at) all showing consistent downregulation in poor survival (logFC range: -0.97 to -1.08, all FDR < 0.01) . IL6ST encodes gp130, the obligate co-receptor for the entire IL-6 cytokine family, and its multi-probe concordance provides exceptional confidence that impaired JAK-STAT signaling is a core feature of poor prognosis in metastatic breast cancer.
ASS1 (Argininosuccinate Synthase 1) shows the strongest upregulation in poor survival (logFC = +1.36, FDR = 7.64×10⁻³) . As the rate-limiting enzyme in arginine biosynthesis, ASS1 elevation indicates metabolic reprogramming toward anabolic pathways, potentially supporting metastatic colonization but also creating an arginine auxotrophy that could be therapeutically exploited.
BCL2 (BCL2 Apoptosis Regulator) exhibits paradoxical downregulation in poor survival (logFC = -0.80) . Rather than representing tumor suppression, BCL2 loss in this metastatic context reflects enhanced apoptotic susceptibility and loss of cellular homeostasis, as confirmed by pathway enrichment showing dysregulated p53 and extrinsic apoptotic signaling.
Additional key genes include: