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

Oncology. 2021;99(12):766-779. doi: 10.1159/000518955. Epub 2021 Sep 27.

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.

Keywords: Colorectal cancer; Liver metastases; Liver resection; Matrix metalloproteinase-8; Matrix metalloproteinase-9; Myeloperoxidase; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Hepatectomy / methods*
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery*
  • Male
  • Matrix Metalloproteinase 8 / blood*
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Peroxidase / blood*
  • Postoperative Period
  • Preoperative Period
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • MPO protein, human
  • Peroxidase
  • MMP8 protein, human
  • Matrix Metalloproteinase 8
  • MMP9 protein, human
  • Matrix Metalloproteinase 9