Research Papers:
Association of MMP-2, RB and PAI-1 with decreased recurrence-free survival and overall survival in bladder cancer patients
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Abstract
Owen T.M. Chan1,*, Hideki Furuya1,*, Ian Pagano2, Yoshiko Shimizu1,3, Kanani Hokutan1,3, Lars Dyrskjøt4, Jørgen Bjerggaard Jensen5, Per-Uno Malmstrom6, Ulrika Segersten6, Filip Janku7 and Charles J. Rosser1
1Clinical and Translational Research Program University of Hawaii Cancer Center, Honolulu, HI, USA
2Cancer Prevention and Control Program Research Program University of Hawaii Cancer Center, Honolulu, HI, USA
3Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI, USA
4Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
5Department of Urology, Aarhus University Hospital, Aarhus, Denmark
6Departments of Surgical Sciences, Uppsala University, Uppsala, Sweden
7Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
*Co-first authors
Correspondence to:
Charles J. Rosser, email: [email protected]
Keywords: angiogenin, bladder cancer, IHC, MMP-2, PAI-1
Received: May 07, 2017 Accepted: July 12, 2017 Published: September 06, 2017
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.
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