Mediterranean fever (PYRIN) is differentially expressed and up-regulated in the bone metastases of patients with metastatic breast cancer.
To understand the transcriptional nature of metastasis to disparate sites in human breast cancer, we mined published microarray data (1), comparing global gene expression profiles of metastasis to the bones and to the lymph nodes. We discovered that the pattern recognition receptor PYRIN, also known as Mediterranean fever (MEFV), was among the genes whose expression was most different, transcriptome-wide, in bone and lymph node metastases. PYRIN mRNA was present at significantly higher quantities in metastasis to the bone as compared to metastasis to the lymph nodes. Analysis of patient survival data revealed that expression of PYRIN in primary tumors of the breast was correlated with distant metastasis-free survival, in lymph node positive patients but not in lymph node negative patients. PYRIN has functions in innate immune sensing of modifications of RhoGTP and the cytoskeleton by bacterial Type III secretion systems (2, 3) and is modulated by Yersinia pestis (4, 5).