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

Authors Xiao YB, Cai SH, Liu LL, Yang X, Yun JP

Received 28 February 2018

Accepted for publication 23 April 2018

Published 26 June 2018 Volume 2018:10 Pages 1781—1789

DOI https://doi.org/10.2147/CMAR.S166971

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Justinn Cochran

Peer reviewer comments 3

Editor who approved publication: Dr Luzhe Sun


Yong-bo Xiao,1,2,* Shao-hang Cai,1,2,* Li-li Liu,1,2 Xia Yang,1,2 Jing-ping Yun1,2

1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; 2Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China

*These authors contributed equally to this work

Introduction: Hepatocellular 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.
Methods: A 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.
Results: The 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.
Conclusion: Our 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.

Keywords:
peroxisome proliferator-activated receptors α, lipid metabolism, hepatocellular carcinoma, prognostic biomarker

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