SMAD2 and neoplasm: It is reported that after sorafenib treatment—the only treatment option for unresectable and advanced HCC, oncogenes were prone to hypermethylation, and the tumor suppressor genes were apt to be hypomethylated in human-derived hepatoma cell line (HA22T/VGH), such as the hypermethylation of Janus kinase (JAK1) gene and the hypomethylation of SMAD family member 2 (SMAD2) gene [24].