Our results reveal alterations in several cancer-related pathways as well as key hub genes, including EIF4E, GSK3β, CCNA2, H2AFX, TGFBR1, CREB1, TGFBR1, THOC2, ZMAT3, and STAG2, potentially critical in early HCC transformation and progression. This evidence concerns the gene CREB1 and cancer.