Spexin expression in the human bile duct and perihilar cholangiocarcinoma

The bile duct transports bile fluid from the liver to the gallbladder and small intestine . It contains bioactive peptides, including galanin (GAL) and its receptors (GAL 1–3 -R). Spexin (SPX), a member of the GAL peptide family, activates GAL 2 -R and GAL 3 -R. Its expression in perihilar bile ducts or in perihilar cholangiocarcinoma (pCCA), the most common biliary cancer , is largely unknown. This study investigated SPX expression in healthy, cholestatic, and malignant bile duct tissues. Immunohistochemistry was used to evaluate SPX in healthy (n = 4), peritumoral (PIT) (n = 23) and pCCA (n = 34) tissues. Score values of SPX expression were calculated and statistically analyzed. In healthy and PIT tissues with or without cholestasis , SPX expression was predominantly observed in cholangiocytes and nerve fibers. In pCCA, tumor cells also expressed SPX. SPX levels were similar across healthy, peritumoral, and cholangiocytes/tumor cells. In a small pCCA patient cohort (n = 19), SPX expression did not correlate with tumor grade or patient survival ( p = 0.0838). The substantial expression of SPX in cholangiocytes and nerve fibers in the bile duct indicates that SPX contributes via galaninergic signaling to gall bladder function . The presence of SPX in submucosal nerve fibers suggests a neuromodulatory role, possibly involving bile duct motility. SPX expression did not correlate with survival in pCCA, whereas previous findings on GAL suggest a prognostic value. This highlights the need for joint studies of SPX and GAL in larger cohorts.