However, in many other cases global changes in EpiGs expression were already observed in chronically injured liver tissues and early stages of HCC, such as the increasing induction of EZH2, KDM5B, KDM3A, ZBTB33, MORC4 and SMARCA4, or the progressive downregulation of KDM8, ARID4A, DNMT3L and SMARCA2. These observations further support the notion that epigenetic alterations amplified in cancer can emerge before the onset of tumors [3, 12, 33, 50]. This evidence concerns the gene ZBTB33 and cancer.