Proteomic analysis of clear cell foci in the human liver identifies differential expression of Starch-Binding Domain-Containing Protein 1 (STBD1)

In experimental hepatocarcinogenesis, glycogen-rich clear cell foci (CCF)/pre-neoplastic lesions represent hepatocytes in the progression to liver cell carcinoma. Similar histological and immuno-histological properties of CCF in the human liver suggest that this transition is also relevant in human liver cell carcinogenesis. However, the molecular processes governing carbohydrate metabolism in CCF, and the events leading to carcinogenesis are not well understood.

To address these issues we isolated CCF and unaltered healthy tissue by laser-capture dissection from seven human liver biopsies and subjected these samples to proteomics analyses.

2601 proteins were identified in at least four out of seven samples (control and CCF each). Hierarchical clustering showed that patient-to-patient differences were larger than differences between control and CCF samples. Still, approximately 40 proteins were identified with differential expression in CCF compared to their respective controls. Among these, Starch-Binding Domain-Containing Protein 1 (STBD1) was the only protein with an obvious function in glycogen metabolism and its expression was reduced in CCF compared to healthy tissue. Using immuno-histological analysis, this finding was validated in independent human tissue sections.

Our findings suggest that STBD1, a protein implicated in glycogen degradation via the lysosomal pathway, could play a role in the accumulation of glycogen in CCF and glycogen-rich pre-neoplastic lesions.