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

Abstract

IntroductionHepatocellular carcinoma (HCC) has a close relationship with lipid metabolism. Peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in the regulation of fatty acid oxidation in the liver. However, the role of PPARα in HCC remains unclear.MethodsA total of 804 HCC specimens were collected to construct a tissue microarray and for immunohistochemical analysis. The relationship between PPARα expression and clinical features of HCC patients was analyzed. Kaplan–Meier analysis was conducted to assess the prognostic value of PPARα expression levels.ResultsThe expression of PPARα in HCC was noticeably decreased in HCC tissues. HCC patients with high levels of PPARα 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 PPARα 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 PPARα 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 PPARα expression in the cytoplasm (P<0.001) were found to be independent prognostic variables for overall survival.ConclusionOur data revealed that PPARα expression was decreased in HCC samples. High PPARα 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.

Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma

“…The association between abnormal lipid metabolism and tumorigenesis has attracted increasing attention (8)(9)(10)(11). Tumor cells have altered proliferative and metabolic abilities compared with normal cells (12,13), and the enzymes associated with fatty acid synthesis are upregulated in tumor tissues; this increases fatty acid synthesis and provides the necessary materials and energy to facilitate rapid tumor growth (14,15).…”

Association between abdominal obesity and liver steatosis and fibrosis among patients with chronic hepatitis B measured by Fibroscan

“…It has been suggested that metabolic syndrome is an indicator of advanced liver fibrosis and cirrhosis independent of viral load in CHB patients (14). Metabolic syndrome, comprising T2DM, hypertension, central obesity and dyslipidaemia, is increasingly prevalent worldwide, particularly in Asia (10,33). A dose-response association between the number of components of metabolic syndrome and the risk of advanced fibrosis was observed in CHB patients (10).…”

Diagnostic and Prognostic Values of MANF Expression in Hepatocellular Carcinoma

“…Despite recent therapeutic approaches such as surgical resection, radiofrequency ablation, and orthotropic liver transplantation, the prognosis of HCC remains poor. The metastasis and recurrence of HCC significantly reduce the survival rate and quality of life of HCC patients [5][6][7][8]. Therefore, novel biomarkers will be substantially beneficial for HCC diagnosis and treatment, and outcomes of HCC patients urgently need to be improved.…”