Sa-Ngiamwibool Prakasit, Yoshinari Kouichi, Shizu Ryota, Kongpetch Sarinya, Prawan Auemduan, Senggunprai Laddawan
Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Cancer Diagn Progn. 2025 Jun 30;5(4):529-541. doi: 10.21873/cdp.10467. eCollection 2025 Jul-Aug.
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.
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.
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 (0.042). Elevated FXR expression was also significantly associated with lymph node metastasis (0.006) and advanced tumor stage (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 (0.125).
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.
背景/目的：越来越多的证据表明核受体在癌症的发生和发展中起作用。本研究旨在探讨两种核受体，法尼酯X受体（FXR）和孕烷X受体（PXR）在胆管癌（CCA）组织中的表达及其与临床病理特征的相关性。
采用免疫组织化学方法检测111例CCA切除患者样本中FXR和PXR的表达，并分析其与临床病理参数的相关性。还评估了这些核受体表达对预测患者预后的有效性。
在所有检测样本中均发现FXR和PXR呈阳性，其表达主要定位于细胞质中。胆管内乳头状肿瘤患者的FXR表达显著较低（0.042）。FXR表达升高也与淋巴结转移（0.006）和肿瘤晚期（0.007）显著相关。对数秩检验分析结果显示，患者的生存时间与这两种核受体的表达无关。然而，FXR/PXR表达较低的CCA患者总体生存期往往较长（0.125）。
FXR可能促进CCA进展至更晚期阶段。FXR和PXR表达的预后意义在CCA中似乎具有相关性。这些核受体可能在这种致命疾病的预测和治疗中发挥作用。
