RNA-seq Profiling of Draining and Metastatic Lymph Nodes in HER2-Positive Breast Cancer Identifies POSTN as a Prognostic Marker

HER2-positive breast cancer is aggressive and associated with poorer survival¹. RNA sequencing (RNA-seq) is widely used in translational oncology². We profiled matched tumor-draining (TDLN) and metastatic lymph nodes (TMLN) from six HER2-positive patients by RNA-seq and performed differential expression with DESeq2 using Benjamini–Hochberg control (FDR < 0.05; |log₂FC| ≥ 1)³. We identified 237 differentially expressed genes (182 upregulated; 55 downregulated) enriched for ECM–receptor interaction, PI3K–AKT signaling, focal adhesion, and cholesterol-metabolism pathways. POSTN was among the most upregulated genes and associated with adverse clinicopathologic features and inferior disease-free survival in an independent validation cohort (n = 120)⁴. These findings implicate ECM remodeling and PI3K–AKT signaling in nodal dissemination and nominate POSTN as a candidate prognostic biomarker in HER2-positive breast cancer.