The portrait of liver cancer is shaped by mitochondrial genetics
Mrittika Chattopadhyay, Edmund C. Jenkins, Ana Victoria Lechuga‐Vieco, Kai Nie, Maria Isabel Fiel, Alexander Rialdi, Ernesto Guccione, José Antonio Enrı́quez, Daniela Sia, Amaia Lujambio, Doris Germain
Abstract
-positive mice, invasive liver cancers develop. RNA sequencing (RNA-seq) analysis of the normal liver reveals that, in this subset, the PAPP-A/DDR2/SNAIL axis of invasion pre-exists along with elevated collagen. Since PAPP-A promotes immune evasion, we analyzed the immune signature and found that their livers are immunosuppressed. Further, the PAPP-A signature identifies the immune exhausted subset of hepatocellular carcinoma (HCC) in humans. Our data suggest that mtDNA of normal liver shapes the entire liver cancer portrait upon acquisition of oncogenic mutations.