Abstract
The development of reliable biomarkers has been an urgent issue as well as a hot spot of research on the diagnosis, treatment, and prognostic evaluation of hepatocellular carcinoma (HCC). Here, we established and validated two field cancerization profile-based prognostic signatures (gene expression score [GES] and immune score [IS]) for HCC. Our study confirmed that field cancerization profile-based models outperform conventional models on risk evaluation, offering insights for further studies on prognostic model construction. The nomogram constructed by combining GES, IS, and TNM stage was proved effective in improving the individualized prediction of the overall risk of patients. Distinct peritumoral characteristics were observed in several immune cells (e.g., CD8 T cells and dendritic cells), which might explain the diversified prognosis and clinical benefit of immunotherapy. Moreover, a series of drug targets, prognosis-associated genes, and pathways were identified, which may contribute to molecular mechanism studies as well as therapeutic target development of HCC.