Another potential actor involved in CCA cell proliferation is heparin-binding (HB) EGF released by CAFs, which binds to the EGF receptor (EGFR) on CCA cells, resulting in the activation of signal transducers and activators of transcription 3 (STAT3), promoting tumor cell migration, motility, and invasion [6,38]. This evidence concerns the gene STAT3 and cholangiocarcinoma.