In a previous study, we demonstrated that within the iCCA TME, the matricellular proteins thrombospondin-1 (THBS1) and thrombospondin-2 (THBS2), and the pigment epithelium-derived factor (PEDF), a multifunctional soluble glycoprotein, are highly expressed and secreted by both cancer-associated fibroblasts (CAFs) and tumor cells [82]. This evidence concerns the gene THBS1 and neoplasm.