APE1/Ref-1 expression in vitro demonstrated that APE1/Ref-1 mRNA level was significantly higher (p = 0.0035) in hepatoma cell lines since JHH-6 (11.9 ± 2.51, CI 5.65–18.1) and Huh-7 (2.5 ± 0.81, CI 0.49–4.55) showed respectively a 11.9-fold and 2.5-fold increase in mRNA level with respect to IHH (Fig 2A), with a progressive increase of APE1/Ref-1 gene expression moving from normal hepatocytes to poorly-differentiated cancer cells pointing to an association between APE1/Ref-1 mRNA level and HCC differentiation grading as observed in human tissues. Here, APEX1 is linked to cancer.