Serum Matrix Metalloproteinase-8 and Myeloperoxidase Predict Survival after Resection of Colorectal Liver Metastases

Abstract

Introduction: Matrix metalloproteinases (MMPs) have been extensively studied in several malignancies, and myeloperoxidase (MPO) is a promising new prognostic biomarker. We investigated the prognostic value of MMP-8, MMP-9, and MPO, as well as carcinoembryonic antigen (CEA), CA19-9, and C-reactive protein (CRP) in colorectal cancer with operable liver metastases. Methods: This study included 419 patients who underwent liver resection for colorectal metastases at the Helsinki University Hospital between 2000 and 2013. Serum samples were drawn before and 3 months after liver resection. We evaluated associations of MMP-8, MMP-9, MPO, CRP, CEA, and CA19-9 concentrations to disease-free survival (DFS) and overall survival (OS) using the Cox proportional hazards model and Kaplan-Meier log-rank method. Results: In univariate Cox regression analyses, pre- and postoperatively high MMP-8 (HR 1.53, 95% CI: 1.07–2.19, p = 0.021 and HR 1.45, 95% CI: 1.01–2.09, p = 0.044, respectively) associated with worse 10-year OS. Postoperatively high MPO indicated better 5-year DFS (HR 0.70, 95% CI: 0.54–0.90, p = 0.007). Elevated pre- and postoperative CEA and CA19-9 as well as postoperative CRP indicated impaired survival. Conclusions: Pre- and postoperatively high MMP-8 associates with worse 10-year OS, and postoperatively high MPO associates with better 5-year DFS. CEA, CA19-9, and CRP are also prognostic.