Early detection of liver cancer – the role of extracellular matrix proteins

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide, primarily linked to chronic liver damage such as fibrosis and cirrhosis. During cirrhosis, activated hepatic stellate cells cause changes in the extracellular matrix. In general, it is unresolved why patients with liver cirrhosis cross the tipping point towards HCC and why some patients are affected earlier than others. To determine proteomic parameters that correlate with structural changes in human cirrhotic liver tissue and therefore could be used for the early detection of HCC, we employed a data-independent acquisition mass spectrometry approach. In addition to analyzing patient-derived liver tissue, we utilized this approach for the analysis of the blood proteome of cirrhotic patients with the aim to identify HCC-relevant signatures. For the large-scale mass spectrometric analysis of human serum and plasma, we developed a standardized protocol that includes automated sample preparation and a screening step to assess sample quality and comparability. Based on this protocol, we were able to determine the extent to which the proteomic information between serum and plasma samples differs. The initial analysis of proteomic changes in longitudinal serum samples from cirrhotic patients who developed HCC during the observation time provided first evidence for HCC-dependent protein clusters.