Posted: Thursday, August 17, 2023
A recent article published in Science Advances highlighted the proteins and metabolites unique to fibrolamellar hepatocellular tumors and shed new insight into how these molecular changes may perpetuate the ammonia spikes that are characteristic of this disease. Sanford M. Simon, PhD, of The Rockefeller University, New York, and colleagues used mass spectrometry to probe the proteome and metabolome of fibrolamellar hepatocellular carcinoma to uncover differences that might explain the pathology of this disease. Their findings revealed that many of the enzymes that produce ammonia are increased and those that consume ammonia are decreased.
“We’re seeing a very distinctive change in the proteins of the cancer cells…. [O]ur observations help explain some of the physiological changes in fibrolamellar [tumors] and also some of the pathological changes—including high levels of ammonia, which is a leading cause of death in fibrolamellar carcinoma,” said Dr. Simon in a recent Rockefeller University press release.
Fibrolamellar hepatocellular tumor and adjacent nontransformed (normal) liver samples were collected from 11 patients and used in this study. Samples were resected and quick-frozen to minimize postsurgical alterations. Tissue samples were then prepared for mass spectrometry analysis of peptides and metabolites. The two types of mass spectrometry performed included label-free quantification and tandem mass tag multiplexing. Tumor proteins involved in glycolysis and hyperammonemic encephalopathy were also investigated.
Findings revealed a total of 4,098 different proteins were detected in the label-free quantification analysis, and a total of 4,650 proteins were detected in the tandem mass tag multiplexing analysis. Analyses also revealed that the greatest protein differences between tumor and normal tissue were in mitochondrial proteins. In addition, there were alterations in proteins involved in ammonia metabolism—specifically, decreases in ornithine carbamoyl transferase with concomitant changes in metabolites known to accumulate in ornithine carbamoyl transferase deficiency. Decreases in glutamine synthetase, the second major pathway in the liver responsible for ammonia clearance, were also found.
Disclosure: The study authors reported no conflicts of interest.