Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival.

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Abstrakt

Tytuł:: Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival.
Autorzy:: Joseph C; Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
Alsaleem M; Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.; Faculty of Applied Medical Sciences, Onizah Community College, Qassim University, Qassim, Saudi Arabia.
Orah N; Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
Narasimha PL; Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
Miligy IM; Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
Kurozumi S; Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
Ellis IO; Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
Mongan NP; Department of Pharmacology, Weill Cornell Medicine, New York, 10065, USA.; Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, LE12 5RD, UK.
Green AR; Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
Rakha EA; Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham, UK. .; Histopathology Department, Faculty of Medicine, Menoufia University, Shibin El Kom, Egypt. .; Division of Cancer and Stem Cells, Department of Histopathology, School of Medicine, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, NG5 1PB, UK. .
Źródło:: Breast cancer research and treatment [Breast Cancer Res Treat] 2020 Jul; Vol. 182 (2), pp. 267-282. Date of Electronic Publication: 2020 May 22.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: Dordrecht : Kluwer Academic
Original Publication: The Hague ; Boston : M. Nijhoff, c1981-
MeSH Terms:: Biomarkers, Tumor/*metabolism
Breast/*metabolism
Breast/*pathology
Breast Neoplasms/*mortality
Matrix Metalloproteinase 9/*metabolism
Biomarkers, Tumor/analysis ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Disease Progression ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Matrix Metalloproteinase 9/analysis ; Matrix Metalloproteinase 9/genetics ; Middle Aged ; Neoplasm Invasiveness/pathology ; Prognosis ; Prospective Studies ; RNA, Messenger/metabolism ; Time Factors ; Tissue Array Analysis
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Contributed Indexing:: Keywords: Breast cancer; ECM remodelling; MMP9; Prognosis
Substance Nomenclature:: 0 (Biomarkers, Tumor)
0 (RNA, Messenger)
EC 3.4.24.35 (MMP9 protein, human)
EC 3.4.24.35 (Matrix Metalloproteinase 9)
Entry Date(s):: Date Created: 20200524 Date Completed: 20210111 Latest Revision: 20210111
Update Code:: 20240105
PubMed Central ID:: PMC7297818
DOI:: 10.1007/s10549-020-05670-x
PMID:: 32445177
: Czasopismo naukowe

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Purpose: MMP9 is a matricellular protein associated with extracellular matrix (ECM) remodelling, that promotes tumour progression, and modulates the activity of cell adhesion molecules and cytokines. This study aims to assess the prognostic value of MMP9 and its association with cytoskeletal modulators in early-stage invasive breast cancer (BC).
Methods: MMP9 expression was evaluated by immunohistochemistry using a well-characterised series of primary BC patients with long-term clinical follow-up. Association with clinicopathological factors, patient outcome and ECM remodelling BC-biomarkers were investigated. METABRIC dataset, BC-GenExMiner v4.0 and TCGA were used for the external validation of MMP9 expression. GSEA gene enrichment analyses were used to evaluate MMP9 associated pathways.
Results: MMP9 immunopositivity was observed in the stroma and cytoplasm of BC cells. Elevated MMP9 protein levels were associated with high tumour grade, high Nottingham Prognostic Index, and hormonal receptor negativity. Elevated MMP9 protein expression correlated significantly with cytokeratin 17 (Ck17), Epidermal Growth Factor Receptor (EGFR), proliferation (Ki67) biomarkers, cell surface adhesion receptor (CD44) and cell division control protein 42 (CDC42). Cytoplasmic MMP9 expression was an independent prognostic factor associated with shorter BC-specific survival. In the external validation cohorts, MMP9 expression was also associated with poor patients' outcome. Transcriptomic analysis confirmed a positive association between MMP9 and ECM remodelling biomarkers. GSEA analysis supports MMP9 association with ECM and cytoskeletal pathways.
Conclusion: This study provides evidence for the prognostic value of MMP9 in BC. Further functional studies to decipher the role of MMP9 and its association with cytoskeletal modulators in BC progression are warranted.

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