Multiomics Integration Reveals the Landscape of Prometastasis Metabolism in Hepatocellular Carcinoma

The systematic investigation of gene mutation and expression is important to discover novel biomarkers and therapeutic targets in cancers. Here, we integrated genomics, transcriptomics, proteomics, and metabolomics to analyze three hepatocellular carcinoma (HCC) cell lines with differential metastatic potentials. The results revealed the profile of the prometastasis metabolism potentially associated with HCC metastasis. The multiomic analysis identified 12 genes with variations at multiple levels from three metabolic pathways, including glycolysis, starch, and sucrose metabolism, and glutathione metabolism. Furthermore, uridine diphosphate (UDP)-glucose pyrophosphorylase 2 (UGP2), was observed to be persistently up-regulated with increased metastatic potential. UGP2 overexpression promoted cell migration and invasion and enhanced glycogenesis in vitro. The role of UGP2 in metastasis was further confirmed using a tumor xenograft mouse model. Taken together, the compendium of multiomic data provides valuable insights in understanding the roles of shifted cellular metabolism in HCC metastasis.