Induction of stemness features and activation of prognostically adverse genomic alterations in hepatocellular carcinoma by field cancerization

Background: HCC is a paradigm for inflammatory cancers. A pre-existing chronic liver damage creates an adverse microenvironment that promotes tumor-initiation and progression. The cancer stem cell origin provides a plausible explanation for the resulting phenotypic heterogeneity of hepatocellular cancers. However, despite profound therapeutic implications the prognostic relevance of CSCs and their cellular localization within the tumor formation remain controversial. Methods: Expression levels and localization of established CSC markers were assessed in pre-neoplastic lesions and two independent cohorts of HCC p…