Semaphorin 3A is a differentially expressed gene in both lymph node and brain metastases in human breast cancer.
Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that semaphorin 3A, encoded by SEMA3A, was among the genes whose expression was most quantitatively different in the brain metastases of patients with metastatic breast cancer. SEMA3A mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of SEMA3A in primary tumors was significantly correlated with patient distant metastasis-free survival in patients with breast cancer. Modulation of SEMA3A expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain.