IRG signature is correlated to clinical trastuzumab resistance in HER2+ BC patients. (A) Illustration showing sample preparation for RNA-seq analysis. Gene set enrichment analysis shows IFN-γ pathway as one of the top gene pathways down-regulated in relapse-metastasis samples (n = 7) compared to primary HER2+ tumors (n = 13). (B) Heatmap showing 104 IRG comprised of 81 ISG, and 23 APP genes that were differentially expressed in metastatic tumors compared to primary tumors (log fold cutoff >1, P < 0.05). (C) Lower expression of IRG is strongly associated with poorer overall survival (OS), distant metastasis-free survival (DMFS), and recurrence-free survival (RFS) in HER2+ BC. Data were collected from GOBO analysis (co.bmc.lu.se/gobo/). Datasets were stratified into three quantiles based on IRG expression (lower, medium, and upper quartile) and censored for 10-y follow-up. Log-rank P values are shown as −log10(P value). (D) Kaplan–Meier plots showing prognostic values of IRG for OS in basal, luminal A and luminal B BC subtypes.