Integrated proteogenomic analysis revealed the metabolic heterogeneity in noncancerous liver tissues of patients with hepatocellular carcinoma.

Understanding the adjacent liver microenvironment of hepatocellular carcinoma (HCC) with possible metastasis tendency might provide a strategy for risk classification of patients and potential therapies by converting the unique metastasis-inclined microenvironment to a metastasis-averse one. In this study, we performed an integrated proteogenomic analysis to have a comprehensive view on the heterogeneity of hepatic microenvironment contributing to HCC metastasis. Pairing mRNA-protein analysis revealed consistent and discordant mRNA-protein expressions in metabolism regulations and cancer-related pathways, respectively. Proteomic profiling identified three subgroups associated with the recurrence-free survival of patients. These proteomic subgroups demonstrated distinct features in metabolic reprogramming, which was potentially modified by epigenetic alterations. This study raises the point of metabolic heterogeneity in HCC noncancerous tissues and may offer a new perspective on HCC treatment.