Characterization of the cellular expression pattern of bile acid receptors in intrahepatic cholangiocellular carcinoma

Cholangiocellular carcinoma (CCA) arises from the epithelial cells of the bile ducts and can be classified according to its location along the biliary tree as intrahepatic (iCCA), perihilar or distal. Each subtype has a distinct epidemiology, biology, prognosis, and strategy for clinical management.

Pathogenesis remains elusive, and only recently, bile acids (BA) as potent signalling molecules have been linked to CCA development. Nevertheless, the spatial expression pattern of the different bile acid receptors in human CCA and adjacent non-tumour tissue is unknown. However, this knowledge could be the cornerstone of potential new bile acid receptor-associated therapeutic strategies in CCA.

In our project, we want to study the tumour microenvironment of iCCA and adjacent non-tumorous tissue with special regard to the cellular expression pattern of bile acid receptors by using Multiplex immunostaining. This technique is a sequential immunostaining protocol consisting of repetitive cycles of staining and chemically induced antibody stripping followed by image processing, allowing the study of up to 10-20 targets simultaneously on one Formalin-fixed paraffin embedded (FFPE) tissue section. Ultimately, we aim to correlate our experimental findings with clinical parameters such as therapy response or survival of the patients. First results indicate an overexpression of TGR5 (GPBAR1), a G-protein-coupled receptor responsive to BA, in CCA tissue.

Publication History

Article published online:
23 January 2024