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. 2017 Sep 6;8(59):99707-99721.
doi: 10.18632/oncotarget.20686. eCollection 2017 Nov 21.

Association of MMP-2, RB and PAI-1 with decreased recurrence-free survival and overall survival in bladder cancer patients

Owen T M Chan  1 , Hideki Furuya  1 , Ian Pagano  2 , Yoshiko Shimizu  1   3 , Kanani Hokutan  1   3 , Lars Dyrskjøt  4 , Jørgen Bjerggaard Jensen  5 , Per-Uno Malmstrom  6 , Ulrika Segersten  6 , Filip Janku  7 , Charles J Rosser  1
Affiliations

Association of MMP-2, RB and PAI-1 with decreased recurrence-free survival and overall survival in bladder cancer patients

Owen T M Chan et al. Oncotarget. .

Abstract

Background: We previously reported an accurate urine-based bladder cancer (BCa)-associated diagnostic signature that can be used to non-invasively detect BCa. In this study, we investigated whether a component of this signature could risk stratify patients with BCa.

Methods: Utilizing immunohistochemistry, we investigated angiogenin, MMP-2, p53, RB and PAI-1 expression from 939 patients with BCa. The expression levels were scored by assigning a proportion score and an intensity score to yield a total staining score for each protein. The expressions of each protein individually and as an aggregate were then correlated with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS).

Results: Differential expressions of these markers were noted in BCa. With multivariate analysis in non-muscle invasive bladder cancer (NMIBC) age, tumor grade portended a worse PFS, while age, tumor grade, nodal status, MMP2, RB and PAI-1 expression portended a worse OS. As for multivariate analysis in muscle invasive bladder cancer (MIBC), age MMP-2 and RB were associated with a worse PFS, while age, nodal status, MMP-2, RB and PAI-1 were associated with a worse OS. Using Kaplan-Meier survival analysis, we noted a significant reduction in OS as more of the five biomarkers were expressed in a tumor. Thus, overall, high expressions of MMP-2, RB and/or PAI-1 in bladder tumors were markers of poor prognosis.

Conclusion: Individually, MMP-2, RB and PAI-1, as well as in aggregate correlated with poor survival in patients with BCa. Thus, patients whose bladder tumors express these biomarkers may benefit from early radical treatment and/or neoadjuvant or adjuvant therapies.

Keywords: IHC; MMP-2; PAI-1; angiogenin; bladder cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST All authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Representative expression status for ANG, MMP-2, p53, RB and PAI-1 in a high-grade non-muscle invasive bladder cancer
Upper row represents high intensity while lower row represents low intensity associated with each target. All images were captured at 400× magnification.
Figure 2
Figure 2. Progression-free survival analysis of 939 patients with bladder cancer
Progression-free survival according to immunostaining status of ANG, MMP-2, p53, RB and PAI-1 in NMIBC (A) and MIBC (B).
Figure 3
Figure 3. Overall survival analysis of 939 patients with bladder cancer
Overall survival according to immunostaining status of ANG, MMP-2, p53, RB and PAI-1 in NMIBC (A) and MIBC (B).
See this image and copyright information in PMC

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