Dynamics of the oncofetal ecosystem during Hepatocellular carcinoma evolution

Abstract

This study uses single-cell RNA sequencing to analyse early- and late-stage hepatocellular carcinoma (HCC) patient samples, revealing an enrichment of oncofetal populations and exhausted CD8+ T cells in late-stage HCC. Cell-cell interaction analyses identified VEGFA signalling by hepatocytes and CXCL12-CXCR4 signalling by oncofetal populations as key drivers of tumour progression. These interactions may initiate oncofetal reprogramming in the tumour microenvironment, with findings validated by spatial assay, highlighting potential therapeutic targets in advanced HCC.