Signaling pathway analyses of respective L-R pairs showed increased outgoing collagen, osteopontin (SPP1), fibronectin, and thrombospondin signaling from CSCs in PC (Figure 2E and Supplemental Figure 2, A and B), which are already known to be associated with dedifferentiation, stem cell support, and metastasis (23–28). This evidence concerns the gene SPP1 and pachyonychia congenita.