The accessory protein of the IL-18 receptor, IL-18 RAP, 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, 2), comparing global gene expression profiles of metastasis to the bones and to the lymph nodes. We discovered that the IL-18 receptor accessory protein, encoded by IL18RAP, was among the genes whose expression was most different, transcriptome-wide, in bone and lymph node metastases. IL18RAP 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 IL18RAP in primary tumors of the breast was correlated with overall survival, in lymph node negative patients but not in lymph node positive patients. Signal transduction through the IL-18 receptor may be important in understanding basic differences between the transcriptional composition of metastasis to the lymph nodes and to the bones in humans with metastatic breast cancer.