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Expression of protease activating receptor-2 (PAR-2) is positively correlated with the recurrence of non-muscle invasive bladder cancer: an immunohistochemical analysis

Authors Nakahara K, Yamasaki K, Nagai T, Fujii M, Akioka T, Takamori H, Terada N, Mukai S, Sato Y, Kamoto T

Received 25 December 2018

Accepted for publication 4 February 2019

Published 11 April 2019 Volume 2019:11 Pages 97—104

DOI https://doi.org/10.2147/RRU.S199512

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Jan Colli


Kozue Nakahara,1 Koji Yamasaki,1 Takahiro Nagai,1 Masato Fujii,1 Takahiro Akioka,1 Hiroki Takamori,1 Naoki Terada,1 Shoichiro Mukai,1 Yuichiro Sato,2 Toshiyuki Kamoto1

1Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; 2Section of Diagnostic Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

Background: Matriptase, which is a Type II transmembrane serine protease, has the potential to activate several growth factors, including pro-hepatocyte growth factor (HGF). A G protein-coupled transmembrane cell-surface receptor and a protease-activated receptor 2 (PAR-2) are also required for activation by matriptase. Activation of PAR-2 has been reported to induce the progression of various cancers. In a previous study, we evaluated the correlation between upregulation of MET phosphorylation with high matriptase expression and worse prognosis in patients with muscle invasive bladder cancer; however, expression of PAR-2, matriptase and MET in non-muscle invasive bladder cancer (NMIBC) has not been evaluated.
Materials and methods: We retrospectively analyzed the expression of PAR-2, matriptase and MET using 55 paraffin-embedded specimens obtained from patients with NMIBC by immunohistochemistry.
Results: MET was significantly expressed in high-grade urothelial carcinoma (UC) and pathological T1 cancers. High expression of PAR-2 was significantly associated with a worse recurrence rate in NMIBC. In subgroup analysis, the expression of PAR-2 was also correlated with high recurrence rate in low-grade UC. In addition, expression of matriptase tended to correlate with worse recurrence rate in high-grade UC.
Conclusion: Increased expression of PAR-2 was significantly correlated with worse recurrence rate in patients with NMIBC. In addition, expression of matriptase also indicated a tendency toward recurrence in high-grade UC, suggesting an important role of matriptase-induced PAR-2 activation in NMIBC.

Keywords: PAR-2, matriptase, MET, NMIBC


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