Cargando…

Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied...

Descripción completa

Detalles Bibliográficos
Autores principales: Kaasinen, Mirjami, Hagström, Jaana, Mustonen, Harri, Sorsa, Timo, Sund, Malin, Haglund, Caj, Seppänen, Hanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951094/
https://www.ncbi.nlm.nih.gov/pubmed/35328734
http://dx.doi.org/10.3390/ijms23063314
_version_ 1784675301029052416
author Kaasinen, Mirjami
Hagström, Jaana
Mustonen, Harri
Sorsa, Timo
Sund, Malin
Haglund, Caj
Seppänen, Hanna
author_facet Kaasinen, Mirjami
Hagström, Jaana
Mustonen, Harri
Sorsa, Timo
Sund, Malin
Haglund, Caj
Seppänen, Hanna
author_sort Kaasinen, Mirjami
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied prognostic role in cancers of the gastrointestinal tract. We examined the prognostic value of MMP-8 immunoexpression in tumour tissue and the amount of MMP-8-positive polymorphonuclear cells (PMNs) in PDAC and their association with immune responses using C-reactive protein (CRP) as a marker of systemic inflammation. Tumour samples from 141 PDAC patients undergoing surgery in 2002–2011 at the Department of Surgery, Helsinki University Hospital were stained immunohistochemically, for which we evaluated MMP-8 expression in cancer cells and the amount of MMP-8-positive PMNs. We assessed survival using the Kaplan–Meier analysis while uni- and multivariable analyses relied on the Cox proportional hazards model. A negative MMP-8 stain and elevated CRP level predicted a poor prognosis (hazard ratio [HR] = 6.95; 95% confidence interval (CI) 2.69–17.93; p < 0.001) compared to a positive stain and low CRP level (<10 mg/L). The absence of PMNs together with an elevated CRP level also predicted an unfavourable outcome (HR = 3.17; 95% CI 1.60–6.30; p = 0.001). MMP-8 expression in the tumour served as an independent positive prognostic factor (HR = 0.33; 95% CI 0.16–0.68; p = 0.003). Tumour MMP-8 expression and a low CRP level may predict a favourable outcome in PDAC with similar results for MMP-8-positive PMNs and low CRP levels. Tumoural MMP-8 expression represents an independent positive prognostic factor in PDAC.
format Online
Article
Text
id pubmed-8951094
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89510942022-03-26 Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma Kaasinen, Mirjami Hagström, Jaana Mustonen, Harri Sorsa, Timo Sund, Malin Haglund, Caj Seppänen, Hanna Int J Mol Sci Article Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied prognostic role in cancers of the gastrointestinal tract. We examined the prognostic value of MMP-8 immunoexpression in tumour tissue and the amount of MMP-8-positive polymorphonuclear cells (PMNs) in PDAC and their association with immune responses using C-reactive protein (CRP) as a marker of systemic inflammation. Tumour samples from 141 PDAC patients undergoing surgery in 2002–2011 at the Department of Surgery, Helsinki University Hospital were stained immunohistochemically, for which we evaluated MMP-8 expression in cancer cells and the amount of MMP-8-positive PMNs. We assessed survival using the Kaplan–Meier analysis while uni- and multivariable analyses relied on the Cox proportional hazards model. A negative MMP-8 stain and elevated CRP level predicted a poor prognosis (hazard ratio [HR] = 6.95; 95% confidence interval (CI) 2.69–17.93; p < 0.001) compared to a positive stain and low CRP level (<10 mg/L). The absence of PMNs together with an elevated CRP level also predicted an unfavourable outcome (HR = 3.17; 95% CI 1.60–6.30; p = 0.001). MMP-8 expression in the tumour served as an independent positive prognostic factor (HR = 0.33; 95% CI 0.16–0.68; p = 0.003). Tumour MMP-8 expression and a low CRP level may predict a favourable outcome in PDAC with similar results for MMP-8-positive PMNs and low CRP levels. Tumoural MMP-8 expression represents an independent positive prognostic factor in PDAC. MDPI 2022-03-18 /pmc/articles/PMC8951094/ /pubmed/35328734 http://dx.doi.org/10.3390/ijms23063314 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kaasinen, Mirjami
Hagström, Jaana
Mustonen, Harri
Sorsa, Timo
Sund, Malin
Haglund, Caj
Seppänen, Hanna
Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma
title Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma
title_full Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma
title_fullStr Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma
title_full_unstemmed Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma
title_short Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma
title_sort matrix metalloproteinase 8 expression in a tumour predicts a favourable prognosis in pancreatic ductal adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951094/
https://www.ncbi.nlm.nih.gov/pubmed/35328734
http://dx.doi.org/10.3390/ijms23063314
work_keys_str_mv AT kaasinenmirjami matrixmetalloproteinase8expressioninatumourpredictsafavourableprognosisinpancreaticductaladenocarcinoma
AT hagstromjaana matrixmetalloproteinase8expressioninatumourpredictsafavourableprognosisinpancreaticductaladenocarcinoma
AT mustonenharri matrixmetalloproteinase8expressioninatumourpredictsafavourableprognosisinpancreaticductaladenocarcinoma
AT sorsatimo matrixmetalloproteinase8expressioninatumourpredictsafavourableprognosisinpancreaticductaladenocarcinoma
AT sundmalin matrixmetalloproteinase8expressioninatumourpredictsafavourableprognosisinpancreaticductaladenocarcinoma
AT haglundcaj matrixmetalloproteinase8expressioninatumourpredictsafavourableprognosisinpancreaticductaladenocarcinoma
AT seppanenhanna matrixmetalloproteinase8expressioninatumourpredictsafavourableprognosisinpancreaticductaladenocarcinoma