Decreased expression of peroxisome proliferator-activated receptor alpha indicates unfavorable outcomes in hepatocellular carcinoma

Introduction: Hepatocellular carcinoma (HCC) has a close relationship with lipid metabolism. Peroxisome proliferator-activated receptor a (PPAR alpha) plays a crucial role in the regulation of fatty acid oxidation in the liver. However, the role of PPAR alpha in HCC remains unclear. Methods: A total of 804 HCC specimens were collected to construct a tissue microarray and for immunohistochemical analysis. The relationship between PPAR alpha expression and clinical features of HCC patients was analyzed. Kaplan-Meier analysis was conducted to assess the prognostic value of PPAR alpha expression levels. Results: The expression of PPAR alpha in HCC was noticeably decreased in HCC tissues. HCC patients with high levels of PPAR alpha expression in cytoplasm had smaller tumors (P=0.027), less vascular invasion (P=0.049), and a higher proportion of complete involucrum (P=0.038). Kaplan-Meier analysis showed that HCC patients with low PPAR alpha expression in the cytoplasm had significantly worse outcomes in terms of overall survival (P<0.001), disease-free survival (P=0.024), and the probability of recurrence (P=0.037). Similarly, overall survival was significantly shorter in HCC patients with negative PPAR alpha expression in the nucleus (P=0.034). Multivariate Cox analyses indicated that tumor size (P=0.001), TNM stage (P<0.001), vascular invasion (P<0.001), and PPAR alpha expression in the cytoplasm (P<0.001) were found to be independent prognostic variables for overall survival. Conclusion: Our data revealed that PPAR alpha expression was decreased in HCC samples. High PPAR alpha expression was correlated with longer survival times in HCC patients, and served as an independent factor for better outcomes. Our study therefore provides a promising biomarker for prognostic prediction and a potential therapeutic target for HCC.