In a separate cluster PF2 we observed several nodes related to the Ras signaling pathway (Fig. 2B), comprising epidermal, fibroblast, nerve, vascular endothelial, insulin-like and platelet-derived growth factors, associated with signaling molecules through Src, MAPK, and PI3K. Fibroblast related pathways were found in cluster PF6 linked to transforming growth factor (TGF)-beta and Wnt signaling pathway (cluster PF3), which included the secreted frizzled related proteins SFRP1 and SFRP2. SFRP1 and 2 are Wnt inhibitors which show reduced expression in RA [28, 29] synovium. This evidence concerns the gene SPAG17 and rheumatoid arthritis.