Abstract

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are major primary liver cancers in adults, comprising liver cancer spectrum. The existence of combined hepatocellular-cholangiocarcinoma (CHC), a histopathologic intermediate form between HCC and CC, suggests phenotypic overlap between these tumors. By applying an integrative oncogenomic approach, we identified a novel HCC subtype, i.e., cholangiocarcinoma-like HCC (CLHCC), which expressed cholangiocarcinoma-like traits (CC signature). In addition, we found that CLHCC coexpressed embryonic stem cell–like expression traits (ES signature) suggesting its derivation from bipotent hepatic progenitor cells. Further histopathological evaluation revealed a variant HCC with fibrous stromal component, i.e. scirrhous HCC, has CC-like genomic features, suggesting that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene expression trait in HCC. Our integrative analysis combining histopathological and genomic data would be a powerful approach to delineate the tumor heterogeneity.

• Keywords: Cholangiocarcinoma-like HCC;Scirrhous type;Stemness