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Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma
Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Oral Pathology and Radiology, University of Turku, Turku, Finland; Translational Cancer Medicine Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Translational Cancer Medicine Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Section of Periodontology and Dental Prevention, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Solna, Sweden.
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2022 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 6, article id 3314Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI, 2022. Vol. 23, no 6, article id 3314
Keywords [en]
C-reactive protein, Matrix metalloproteinase 8, Pancreatic cancer, Polymorphonuclear cell
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-193405DOI: 10.3390/ijms23063314ISI: 000775291400001Scopus ID: 2-s2.0-85126720785OAI: oai:DiVA.org:umu-193405DiVA, id: diva2:1648610
Available from: 2022-03-31 Created: 2022-03-31 Last updated: 2023-09-05Bibliographically approved

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