A multiplexed, particle-based flow cytometric assay identified plasma matrix metalloproteinase-7 to be associated with cancer-related death among patients with bladder cancer

Abstract

BACKGROUND: The current study was conducted to demonstrate the utility of a multiplexed, particle-based flow cytometric assay for the simultaneous analysis of a panel of matrix metalloproteinases (MMPs) using small volumes of plasma samples from patients with bladder cancer. In addition, the authors attempted to test the hypothesis that plasma levels of MMPs are associated with time to cancer-related death. METHODS: Plasma MMP concentrations (MMP-1, -2, -3, -7, -8, -9, and -12) in 135 patients presenting with high-grade ≥T1 bladder cancer were measured. Data regarding clinical and pathologic features was ascertained in a retrospective fashion. RESULTS: The median duration of follow-up was 30.4 months. At the time of analysis, 61 patients had died, including 45 (33.3%) who died of bladder cancer. Plasma MMP-12 was not measurable. For all other MMPs, the intra-assay coefficient of variation varied from 6.12% to 9.82%. MMP-1, -2, -3, -8, and -9 were not found to be significantly associated with time to cancer-related death. Plasma MMP-7 levels were significantly associated with time to cancer-related death after adjustment for competing clinical and pathologic features (hazard ratio [HR], 2.2; 95% confidence interval [95% CI], 1.1-4.5 [P = .022]). The 5-year median cancer-specific survival rates for those patients with MMP-7 levels above and below the median value (300 pg/mL) were 73.6% (95% CI, 60.0-83.2%) and 48.0% (95% CI, 32.5-61.9%), respectively (P = .01). CONCLUSIONS: Multiplexed, particle-based flow cytometric assay allows for the high-throughput measurement of multiple plasma or serum proteins simultaneously. By using this new technology in a cohort of patients with bladder cancer, plasma levels of MMP-7 were identified as being significantly associated with time to cancer-related death. © 2010 American Cancer Society.