Network Analysis Reveals Heterogeneous Response of Redox Metabolism in Hepatocellular Carcinoma Patients
48 Pages Posted: 18 Jul 2018 Sneak Peek Status: Under ReviewMore...
Redox metabolism is often considered for cancer treatment but a systematic examination of redox behavior in hepatocellular carcinoma (HCC) is missing. We employed systems biology approaches to identify key features in redox metabolism in HCC. Several redox genes, including novel prognostic markers, are co-expressed with liver-specific, immune and inflammation genes. HCC also display antagonistic redox behavior, associated with altered fatty acid and amino acid metabolisms, differentiation, proliferation, and antioxidant defense. These responses are observed at the transcriptomic, metabolomic and protein levels, validated in independent cohorts, and experimentally observed using mice transcriptomics. Our integrative approach highlights mechanistic differences associated with HCC subtypes and progression, enabling tumor stratification and identification of survival signatures and potential therapeutic targets in redox metabolism.
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