Matrix metalloproteinase-11 as a marker of metastasis and predictor of poor survival in urothelial carcinomas

Wei Ming Li, Yu Ching Wei, Chun Nung Huang, Hung Lung Ke, Ching Chia Li, Hsin Chih Yeh, Lin Li Chang, Chun Hsiung Huang, Chien Feng Li, Wen Jeng Wu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background and Objectives Urothelial carcinomas (UC) of urinary bladder (UB) and upper urinary tract (UT) are heterogeneous diseases with high morbidity and mortality. We looked for genes with metalloendopeptidase activity in a published UBUC transcriptomic database (GSE31684):MMP-11 was the most significant, showing stepwise up-regulation. We analyzed MMP-11 expression and association with clinicopathologic factors and survival in our well-characterized cohort of UCs. Methods We determined MMP-11 expression in 295 UBUCs and 340 UTUCs with immunohistochemistry, evaluated by H-score. In a retrospective study, MMP-11 expression was correlated with clinicopathologic features and with disease-specific survival (DSS) and metastasis-free survival (MeFS). The statistical significance was evaluated with univariate and multivariate analyses. Results High MMP-11 expression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular and perineural invasion, and frequent mitoses. In multivariate Cox regression analyses, which adjusted for standard clinicopathologic characteristics, MMP-11 expression was independently associated with cancer-specific mortality (hazard ratio [HR] in UTUC:3.027, P = 0.005; in UBUC: 2.631, P = 0.010) and with metastasis development (HR in UTUC:2.261, P = 0.018; in UBUC:1.801, P = 0.026). Conclusions MMP-11 overexpression is associated with aggressive tumor phenotype and unfavorable clinical outcome in UTUC and UBUC, suggesting it may serve as a novel prognostic and therapeutic target. J. Surg. Oncol. 2016;113:700-707.

Original languageEnglish (US)
Pages (from-to)700-707
Number of pages8
JournalJournal of Surgical Oncology
Volume113
Issue number6
DOIs
StatePublished - May 1 2016
Externally publishedYes

Keywords

  • bladder cancer
  • MMP-11
  • prognosis
  • upper urinary tract urothelial carcinoma
  • urothelial carcinoma

ASJC Scopus subject areas

  • Surgery
  • Oncology

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    Li, W. M., Wei, Y. C., Huang, C. N., Ke, H. L., Li, C. C., Yeh, H. C., Chang, L. L., Huang, C. H., Li, C. F., & Wu, W. J. (2016). Matrix metalloproteinase-11 as a marker of metastasis and predictor of poor survival in urothelial carcinomas. Journal of Surgical Oncology, 113(6), 700-707. https://doi.org/10.1002/jso.24195