Expression and Prognostic Implication of the Nuclear Receptors Farnesoid X Receptor and Pregnane X Receptor in Human Cholangiocarcinoma.

Abstract

Background/aim: Cumulative evidence reveals the contribution of nuclear receptors in the development and progression of cancers. The present study aimed to investigate the expression of two nuclear receptors, farnesoid X receptor (FXR) and pregnane X receptor (PXR), in cholangiocarcinoma (CCA) tissues and the correlation of their expression with clinicopathological features.

Materials and methods: FXR and PXR expression was evaluated in 111 resected CCA patient samples using immunohistochemistry, and the association of its expression with clinicopathological parameters was analyzed. The effectiveness of the expression of these nuclear receptors in predicting patients' outcomes was also assessed.

Results: FXR and PXR positivity was noted in all examined samples, with their expression predominantly localized in the cytoplasm. Patients with intraductal papillary neoplasm of the bile duct had significantly lower FXR expression (p=0.042). Elevated FXR expression was also significantly associated with lymph node metastasis (p=0.006) and advanced tumor stage (p=0.007). The results of the log-rank test analysis showed that the survival time of the patients was not associated with the expression of these two nuclear receptors. However, the CCA patients presenting low FXR/PXR expression tended to have a longer overall survival (p=0.125).

Conclusion: FXR may contribute to the progression of CCA to more advanced stages. The prognostic significance of FXR and PXR expression appears relevant in CCA. These nuclear receptors may have a function in the prediction and treatment of this deadly disease.