High serum MMP-14 predicts worse survival in gastric cancer

PLoS One. 2018 Dec 7;13(12):e0208800. doi: 10.1371/journal.pone.0208800. eCollection 2018.

Abstract

Matrix metalloproteinases (MMPs), endopeptidases with diverse biochemical functions, can promote cancer cell invasion and metastasis by degrading the extracellular matrix. A high matrix metalloproteinase-14 (MMP-14) expression in gastric cancer tissue has been associated with metastasis and poor prognosis. To further understand this association, we investigated serum MMP-14 as a biomarker in gastric cancer patients. The patient cohort consisted of 240 gastric adenocarcinoma patients who underwent surgery at Helsinki University Hospital, Finland, between 2000 and 2009. We determined the soluble MMP-14 serum levels using an enzyme-linked immunosorbent assay. We then calculated the associations between serum levels and clinicopathologic variables using the Mann-Whitney U-test or the Kruskal-Wallis test. We constructed survival curves using the Kaplan-Meier method and calculating the hazard ratios using the Cox proportional hazard model. We revealed a positive association between a high serum MMP-14 level and stages III-IV (p = 0.029), and between a high serum MMP-14 and distant metastasis (p = 0.022). Patients with a low serum MMP-14 had a 5-year disease-specific survival of 49.2% (95% confidence interval [CI] 45.5-52.9), whereas patients with a high serum MMP-14 had a 5-year survival of 22.1% (95% CI 15.2-29.0; p = 0.001). High serum MMP-14 was a statistically significant prognostic factor among patients with an intestinal type of cancer (hazard ratio [HR] 3.54; 95% CI 1.51-8.33; p = 0.004), but not among patients with a diffuse type. The serum MMP-14 level remained an independent prognostic factor in our multivariate survival analysis (HR 1.55; 95% CI 1.02-2.35; p = 0.040). This study indicates for the first time that high serum soluble MMP-14 levels in gastric cancer serves as a marker for a poor prognosis, possibly indicating the presence of distant metastases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / blood
  • Adenocarcinoma* / mortality
  • Adenocarcinoma* / pathology
  • Aged
  • Biomarkers, Tumor / blood*
  • Disease-Free Survival
  • Female
  • Finland / epidemiology
  • Follow-Up Studies
  • Humans
  • Male
  • Matrix Metalloproteinase 14 / blood*
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / blood*
  • Retrospective Studies
  • Stomach Neoplasms* / blood
  • Stomach Neoplasms* / mortality
  • Stomach Neoplasms* / pathology
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • MMP14 protein, human
  • Matrix Metalloproteinase 14

Associated data

  • Dryad/10.5061/dryad.hb62394

Grants and funding

This study was financially supported by the Faculty of Medicine, University of Helsinki, Helsinki, Finland (CB), Karolinska Institutet, Stockholm, Sweden (TS, TT), Helsinki University Hospital Research Foundation, Helsinki, Finland (TS, TT), Competitive State Research Financing of the Expert Responsibility of Helsinki University Hospital, Helsinki, Finland (CH), the Finnish Cancer Foundation (CH), Finska Läkaresällskapet (CH), and the Sigrid Jusélius Foundation (CH, AK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.