Among five sets of mouse HCC tissues from C3HeB/FeJ male mice, which develop spontaneous HCC at a high frequency [17], we also observed a modest to striking decrease of p-Smad3 in the majority of HCCs (except Mouse 3) in comparison to the normal liver tissue and liver tissue adjacent to HCC (Fig. 1D). Here, SMAD3 is linked to hepatocellular carcinoma.