Galanin System in the Human Bile Duct and Perihilar Cholangiocarcinoma

Background: Perihilar cholangiocarcinoma (pCCA) is characterised by poor outcomes. Early diagnosis is essential for patient survival. The peptide galanin (GAL) and its receptors GAL_1-3 are expressed in various tumours. Detailed characterisation of the GAL system in pCCA is lacking. Our study sought to characterise GAL and GAL_1-3 receptor (GAL_1-3-R) expression in the healthy human bile duct, in cholestasis and pCCA.

Methods: Immunohistochemical staining was performed in healthy controls (n = 5) and in the peritumoural tissues (with and without cholestasis) (n = 20) and tumour tissues of pCCA patients (n = 33) using validated antibodies. The score values of GAL and GAL_1-3-R expression were calculated and statistically evaluated.

Results: GAL and GAL₁-R were expressed in various bile duct cell types. GAL₂-R was only slightly but still expressed in almost all the examined tissues, and GAL₃-R specifically in cholangiocytes and capillaries. In a small pCCA patient cohort (n = 18), high GAL expression correlated with good survival, whereas high GAL₃-R correlated with poor survival.

Conclusions: Our in-depth characterisation of the GAL system in the healthy human biliary duct and pCCA in a small patient cohort revealed that GAL and GAL₃-R expression in tumour cells of pCCA patients could potentially represent suitable biomarkers for survival.