Moreover, ISG15 levels in HCC of different grades and metastatic samples were also studied (GSE195952 & GSE63018),[23, 24] elevated ISG15 was found in low differentiated HCC tissues (grade III/IV) compared with high differentiated HCC tissues (graded I/II, Figure 1N), whereas no significant difference was found between the primary HCC and metastatic tumor samples (Figure S1A, Supporting Information). This evidence concerns the gene ISG15 and metastatic neoplasm.