GDF15 expression correlated with the severity of fibrosis in patients with chronic liver disease[36], [37], [38], [39] and was associated with an increased risk of liver cancer.[40], [41], [42] In ex vivo models based on cell lines (Huh7, LX2 and HepG2), the increase in GDF15 was correlated with activation of these cell lines and production of type 1 collagen via activating ERK1/2 and Smad3 signaling.43 Here, SMAD3 is linked to liver cancer.