GDF15 and cancer: This downregulation could be due to the suppression of HAMP, TfR2, HJV, ALK2 and/or circular RNA circ_0004913, upregulations of matriptase-2 and/or GDF15, and inactivation of RUNX3 and/or mutations in TP53. Regardless, hepcidin downregulation can increase cancer proliferation and exacerbate HCC pathology.