Abstract

Introduction

   Hepatocellular carcinoma is a highly aggressive and heterogeneous
   malignancy with limited understanding of its heterogeneity.

Methods

   In this study, we applied ten multi-omics classification algorithms to
   identify three distinct molecular subtypes of HCC (C1–C3). To further
   explore the immune microenvironment of these molecular subtypes, we
   leveraged single-cell transcriptomic data and employed CIBERSORTx to
   deconvolute their immune landscape.

Results

   Among them, C3 exhibited the worst prognosis, whereas C1 and C2 were
   associated with relatively better clinical outcomes. Patients in the C3
   group exhibited a high burden of copy number variations, mutation load,
   and methylation silencing. Our results revealed that compared to C1 and
   C2, C3 had a lower proportion of hepatocytes but a higher proportion of
   cholangiocytes and macrophages. Through analyses of hepatocyte,
   cholangiocyte, and macrophage subpopulations, we characterized their
   functional states, spatial distribution preferences, evolutionary