Pretreatment serum TIMP-1 levels and survival in advanced pancreatic cancer

Abstract

e15568 Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to have diverse multifunctional roles in tumorigenesis such as inhibition of the catalytic activity of MMPs, growth promotion, inhibition of apoptosis and regulation of angiogenesis. Elevated TIMP-1 has been associated with an unfavorable prognosis in many cancers including breast, colorectal, gastric, head and neck, lung, and lymphoma. VEGF is also intimately associated with angiogenesis. Methods: This study determined serum TIMP-1 and VEGF levels in a phase III clinical trial of 157 patients with advanced pancreatic cancer. ELISAs for TIMP-1 and VEGF (Oncogene Science / Siemens HealthCare Diagnostics, Cambridge, MA) were employed to measure pretreatment serum TIMP-1 levels in 157 pancreatic cancer patients enrolled in a randomized, double-blind, placebo-controlled phase III trial. Statistical analysis was performed with TIMP-1 and VEGF on a continuous and cutpoint basis. Serum biomarker levels were then correlated with patient survival using Kaplan -Meier life table analysis. Results: Serum TIMP-1 levels in 157 pancreatic patients had a median of 409.9 ng/mL, and ranged from 144 to 1078 ng/mL. Patients with higher serum TIMP-1 had significantly shorter survival on a continuous basis (p = 0.001), on quartile analysis (p = 0.004), and on a dichotomous cutpoint analysis of upper 25 % vs lower 75 % (median survival 101 days vs. 197 days)(p< 0.001). Serum VEGF level was not associated with survival on a continuous (p = 0.57) or cutpoint analysis (p= 0.93). Conclusions: Pancreatic cancer patients with higher serum TIMP-1 levels had significantly shorter overall survival. Serum TIMP-1 level should be evaluated as a predictive factor for response to novel treatment regimens. [Table: see text]