Work

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

Year: 2017

Type: article

Abstract: // 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 and Charles J. Rosser 1 1 Clinical and Translational Research Program University of Hawaii Cancer Center, Honolulu, HI, USA 2 Cancer Prevention and Control Program Research Program University of Hawaii Cancer Center, Honolulu, HI, USA 3 Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI, USA 4 Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark 5 Department of Urology, Aarhus University Hospital, Aarhus, Denmark 6 Departments of Surgical Sciences, Uppsala University, Uppsala, Sweden 7 Department 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.20686