Altered Expression of Secreted Mediator Genes That Mediate Aggressive Breast Cancer Metastasis to Distant Organs

Due to the heterogeneous nature of breast cancer, metastasis organotropism has been poorly understood. This study assessed specific cancer-related gene expression changes occurring with metastatic cancer recurrence distant organs compared non-metastatic cancer. We found that several secreted mediators encoding genes notably, LCN2 and S100A8 overexpressed at site spine (LCN2, 5-fold; S100A8, 6-fold) bone 3-fold) vs. primary tumors in syngeneic implantation/tumor-resection mouse model. In contrast, ESM-1 is markedly downregulated sites. Further digging into TCAGA-BRCA, SCAN-B, METABRIC cohorts data analysis revealed LCN2, individual scores were strongly associated disease-specific survival (DSS) cohort (hazard ratio (HR) > 1, p < 0.0004). The predicted worse clinically aggressive tumors, such as high Nottingham histological grade advanced staging. Higher score was overall (OS) triple-negative (TNBC) hormonal receptor (HR)-positive/HER2-negative subtype cohort, HER2+ TCGA-BRCA SCAN-B cohorts. Our suggested prognostic predictive values may be useful for spine, bone, lung metastasis, particularly more subtypes TNBC