Integrative transcriptomic analysis reveals novel targets for personalized medicine across seven metastatic breast cancer subtypes

The greatest cause of death from breast cancer is metastasis, yet little is known about the molecular mechanisms behind this phenomenon. Using four publically accessible datasets, we conducted a thorough transcriptome analysis of 187 samples from seven breast cancer metastatic sites: the brain, bone, lung, liver, lymph nodes, skin, and local-regional skin (skinlr). Of the 12,005 genes that were found to be shared by all samples in this investigation, 604-885 differentially expressed genes (DEGs) were unique to each metastatic location. Pathways including PI3K-Akt signaling, prolactin signaling, complement, and coagulation cascades were identified by functional enrichment analysis as important metastasis drivers with unique functions in different locales. The results of regulatory analysis revealed 77 upstream factors, including 14 kinases (like EPHB3, PAK3) and 63 transcription factors (like ESR1, FOXA1, and GATA3), some of which were discovered for the first time in breast cancer metastases (like TCF4, HOXA10). It was shown that hub genes including MMP9, SPP1, and PDGFRB are essential for the survival and development of metastases, offering new information on site-specific biology. Crucially, by identifying site-specific molecular markers, these discoveries pave the way for personalized medicine techniques and allow tumor-specific therapy tactics, such as targeting Central Carbon Metabolism in lung and skin metastases. This work provides actionable options for tumor-specific treatment and tailored interventions by highlighting new molecular candidates and signaling pathways for metastatic breast cancer.