Elevated circulating pregnane X receptor as a novel diagnostic biomarker in hepatocellular carcinoma

Aim: Hepatocellular carcinoma (HCC) poses a significant global health threat. The pregnane X receptor (PXR) is a central regulator of xenobiotic metabolism and plays a key role in mediating cellular resistance to anti-tumor drugs in HCC. Indeed, the precise role of PXR in HCC pathogenesis remains unclear. This study aimed to investigate blood and hepatic PXR levels and their association with inflammation in HCC patients. Additionally, we assessed the diagnostic potential of PXR in HCC patients compared to control subjects. Methods: Following approval by the Institute Ethical Committee, 40 HCC patients and 40 healthy volunteers were enrolled in this study. Baseline patient characteristics, serum alpha-fetoprotein (AFP), and biochemical parameters were analyzed. Serum levels of PXR, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-1β were measured using ELISA. The hepatic expression of phosphorylated nuclear factor kappa B (NFκB) and PXR proteins was analyzed by western blotting. Results: When compared to control subjects, serum PXR levels were increased in HCC cases (1.34 ± 0.16 vs. 4.09 ± 0.33; P < 0.0001). Similarly, hepatic PXR expression was increased in HCC tissues. Moreover, HCC patients exhibited elevated inflammatory cytokines and a deranged hepatobiliary profile compared to controls. Conclusions: Elevated serum PXR levels in HCC patients were positively correlated with inflammation. Notably, serum PXR demonstrated greater sensitivity and specificity in diagnosing HCC. These findings suggest that PXR may serve as a plausible biomarker in the diagnosis of HCC.