The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy

<i>Background and Objectives</i>: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study a...

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Main Authors: Ming-Chao Tsai, Chih-Che Lin, Ding-Wei Chen, Yueh-Wei Liu, Yi-Ju Wu, Yi-Hao Yen, Pao-Yuan Huang, Chih-Chien Yao, Ching-Hui Chuang, Chang-Chun Hsiao
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Medicina
Subjects:
AFP
Online Access:https://www.mdpi.com/1648-9144/57/6/574
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language English
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author Ming-Chao Tsai
Chih-Che Lin
Ding-Wei Chen
Yueh-Wei Liu
Yi-Ju Wu
Yi-Hao Yen
Pao-Yuan Huang
Chih-Chien Yao
Ching-Hui Chuang
Chang-Chun Hsiao
spellingShingle Ming-Chao Tsai
Chih-Che Lin
Ding-Wei Chen
Yueh-Wei Liu
Yi-Ju Wu
Yi-Hao Yen
Pao-Yuan Huang
Chih-Chien Yao
Ching-Hui Chuang
Chang-Chun Hsiao
The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy
Medicina
PAR2
hepatocellular carcinoma
liver resection
AFP
author_facet Ming-Chao Tsai
Chih-Che Lin
Ding-Wei Chen
Yueh-Wei Liu
Yi-Ju Wu
Yi-Hao Yen
Pao-Yuan Huang
Chih-Chien Yao
Ching-Hui Chuang
Chang-Chun Hsiao
author_sort Ming-Chao Tsai
title The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy
title_short The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy
title_full The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy
title_fullStr The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy
title_full_unstemmed The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy
title_sort role of protease-activated receptor 2 in hepatocellular carcinoma after hepatectomy
publisher MDPI AG
series Medicina
issn 1010-660X
1648-9144
publishDate 2021-06-01
description <i>Background and Objectives</i>: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. <i>Materials and Methods</i>: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. <i>Results</i>: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, <i>p</i> = 0.006), α-fetoprotein (AFP) (HR, 1.696, <i>p</i> = 0.003), liver cirrhosis (HR, 1.735, <i>p</i> = 0.002), and advanced TNM stage (HR, 2.061, <i>p</i> < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, <i>p</i> < 0.001) and histological grade (HR, 2.675, <i>p</i> = 0.002) and high PAR2 expression (HR, 1.832, <i>p</i> = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. <i>Conclusion</i>: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.
topic PAR2
hepatocellular carcinoma
liver resection
AFP
url https://www.mdpi.com/1648-9144/57/6/574
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spelling doaj-a8ee6a9643604a5f9154e37ebd61420f2021-06-30T23:15:52ZengMDPI AGMedicina1010-660X1648-91442021-06-015757457410.3390/medicina57060574The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after HepatectomyMing-Chao Tsai0Chih-Che Lin1Ding-Wei Chen2Yueh-Wei Liu3Yi-Ju Wu4Yi-Hao Yen5Pao-Yuan Huang6Chih-Chien Yao7Ching-Hui Chuang8Chang-Chun Hsiao9Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanLiver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanCenter for Translational Research in Biomedical Sciences, Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanLiver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanLiver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Nursing, Meiho University, Pingtung 91202, TaiwanGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan<i>Background and Objectives</i>: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. <i>Materials and Methods</i>: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. <i>Results</i>: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, <i>p</i> = 0.006), α-fetoprotein (AFP) (HR, 1.696, <i>p</i> = 0.003), liver cirrhosis (HR, 1.735, <i>p</i> = 0.002), and advanced TNM stage (HR, 2.061, <i>p</i> < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, <i>p</i> < 0.001) and histological grade (HR, 2.675, <i>p</i> = 0.002) and high PAR2 expression (HR, 1.832, <i>p</i> = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. <i>Conclusion</i>: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.https://www.mdpi.com/1648-9144/57/6/574PAR2hepatocellular carcinomaliver resectionAFP