Notably, when present in tumours, normal fibroblast subtypes up-regulated activation- (FAP, FN1, PDPN, COL1A1), inflammation- (CXCL1, ISG15) and insulin-like growth factor (IGF)-related (IGF1, IGFBP2, IGFBP4) genes (Supplementary Fig. 3I) suggesting early activation (with these genes expressed at higher levels in CAF clusters). This evidence concerns the gene IGFBP4 and neoplasm.