Fig. 7.

Clinical significance of HNF4A and HIC1 in liver cancer. (A) HNF4A and GSH were elevated while HIC1 and MDA were suppressed in liver cancer compared to paired normal liver tissue. WB was performed in paired liver cancer (T)-normal liver (N) from 10 patients. TMA was also performed to evaluate the HNF4A and HIC1 expression in liver cancer and in the normal liver. (B) HNF4A was positively associated and HIC1was negatively associated with the stage of liver cancer. Representative IHC images of HNF4A and HIC1 were shown. The association between the stage and the expression of HNF4A and HIC1 were analyzed by aχ [2] test. Scale bar, 200 μm. (C) Survival in patients with liver cancer after curative surgery. Patients with different expression levels of HNF4A (left) or HIC1 (right) were analyzed. (D) Survival in WT, HNF4A−/− and HIC1−/− mice with DEN/CCl4 treatment. (n = 20/group) (E) Schematic presentation of the mechanism underlying the interaction between HIC1 and HNF4A to control the balance of FUF and FDF upon stimulation of ferroptosis. The data are shown as the means + SD from three independent experiments. **, p < 0.01 indicate statistical significance. The data were analyzed by a one-way ANOVA test (Fig. 7A lower) and a log rank test (Fig. 7C and D). Images of WB and IHC are representative ones of 3 independent experiments (Fig. 7A, upper left and 7B).