1Laboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
2Proteomics Resource Center, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
3General Surgery Division, Surgery Department, Hospital Nove de Julho, São Paulo, Brazil.
4Lahasky Medical Clinic, Abbeville, LA 70510, USA.
5The Fibrolamellar Registry, New York, NY 10028, USA.
6Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55904, USA.
7Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USA.
Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and pathological alterations in FLC cells, including their drug sensitivity and glycolysis. Hyperammonemic encephalopathy is a recurrent problem in these patients, and established treatments based on the assumption of liver failure are unsuccessful. We show that many of the enzymes that produce ammonia are increased and those that consume ammonia are decreased. We also demonstrate that the metabolites of these enzymes change as expected. Thus, hyperammonemic encephalopathy in FLC may require alternative therapeutics.