Clinical Significance of Sphingosine 1-phosphate Receptor 2 and Takeda G Protein-coupled Receptor 5 in Extrahepatic Cholangiocarcinoma Patients

Background & Aims: In biliary epithelial cells, two bile acid receptors, sphingosine 1-phosphate receptor 2 (S1PR2) and Takeda G protein-coupled receptor 5 (TGR5) have been reported to trigger cell proliferation, as well as neoplastic cell invasiveness. In this study, we aimed to investigate the clinical significance of S1PR2/ TGR5 expression in extrahepatic cholangiocarcinoma (CCA) patients. Methods: Patients who underwent surgical resection of extrahepatic CCA at Korea University Guro Hospital between 2002 and 2018 were included. Data on immunohistochemical staining and H-score of S1PR2 and TGR5 were evaluated using digital image analysis. Results: A total of 115 cases of invasive CCA were analyzed. The H-score of S1PR2 showed a decrease in invasive CCA (p=0.052) but that of TGR5 showed a significant increase (p=0.02). Overall survival and disease-free survival were significantly lower in the low S1PR2 expression group (p<0.05) than in the control group; however, TGR5 expression was not significant (p=0.096). In multivariate analysis, low S1PR2 was only significant for poor prognosis.Conclusion: Low S1PR2 level was the only independent poor prognostic factor in patients with resected extrahepatic CCA.