As tumors progress to advanced stages, TGF-β signaling gradually exhibits pro-tumorigenic effects such as induction of immunosuppressive microenvironment, EMT, and promotion of angiogenesis.283 In HCC, downregulation of the TGF-β signaling pathway may imply loss of cancer suppressive activity, while upregulation leads to fibrosis and inflammation.287 Nearly 40% of HCC patients have somatic mutations in at least one member of the TGF-β pathway.287. This evidence concerns the gene TGFB1 and hepatocellular carcinoma.