High serum MMP-14 predicts worse survival in gastric cancer.

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 pro...

Full description

Bibliographic Details
Main Authors: Aaro Kasurinen, Taina Tervahartiala, Alli Laitinen, Arto Kokkola, Timo Sorsa, Camilla Böckelman, Caj Haglund
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0208800
_version_ 1819128334995423232
author Aaro Kasurinen
Taina Tervahartiala
Alli Laitinen
Arto Kokkola
Timo Sorsa
Camilla Böckelman
Caj Haglund
author_facet Aaro Kasurinen
Taina Tervahartiala
Alli Laitinen
Arto Kokkola
Timo Sorsa
Camilla Böckelman
Caj Haglund
author_sort Aaro Kasurinen
collection DOAJ
description 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.
first_indexed 2024-12-22T08:26:11Z
format Article
id doaj.art-31e1e3dc9c53477d92e350646b55ed7c
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-22T08:26:11Z
publishDate 2018-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-31e1e3dc9c53477d92e350646b55ed7c2022-12-21T18:32:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011312e020880010.1371/journal.pone.0208800High serum MMP-14 predicts worse survival in gastric cancer.Aaro KasurinenTaina TervahartialaAlli LaitinenArto KokkolaTimo SorsaCamilla BöckelmanCaj HaglundMatrix 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.https://doi.org/10.1371/journal.pone.0208800
spellingShingle Aaro Kasurinen
Taina Tervahartiala
Alli Laitinen
Arto Kokkola
Timo Sorsa
Camilla Böckelman
Caj Haglund
High serum MMP-14 predicts worse survival in gastric cancer.
PLoS ONE
title High serum MMP-14 predicts worse survival in gastric cancer.
title_full High serum MMP-14 predicts worse survival in gastric cancer.
title_fullStr High serum MMP-14 predicts worse survival in gastric cancer.
title_full_unstemmed High serum MMP-14 predicts worse survival in gastric cancer.
title_short High serum MMP-14 predicts worse survival in gastric cancer.
title_sort high serum mmp 14 predicts worse survival in gastric cancer
url https://doi.org/10.1371/journal.pone.0208800
work_keys_str_mv AT aarokasurinen highserummmp14predictsworsesurvivalingastriccancer
AT tainatervahartiala highserummmp14predictsworsesurvivalingastriccancer
AT allilaitinen highserummmp14predictsworsesurvivalingastriccancer
AT artokokkola highserummmp14predictsworsesurvivalingastriccancer
AT timosorsa highserummmp14predictsworsesurvivalingastriccancer
AT camillabockelman highserummmp14predictsworsesurvivalingastriccancer
AT cajhaglund highserummmp14predictsworsesurvivalingastriccancer