We concluded that while CAF-SULF2 contributes to the regulation of Glypican-3/Wnt and β-catenin in HCC, supported by in vitro data, the in vivo heterogeneity was in keeping with additional mechanisms contributing to the poor prognosis attributed to CAF-SULF2 in our case series. Here, SULF2 is linked to hepatocellular carcinoma.