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Open Access Green as soon as Postprint is submitted to ZB.
Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple-negative breast cancer.
Biol. Chem. 398, 1151-1164 (2017)
Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER and PR and the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded TNBC tumor tissue specimens. For this, KLK4 protein expression was assessed by immunohistochemistry in primary tumor tissue sections (tissue microarrays) of 188 TNBC patients, mainly treated with anthracycline- or CMF-based polychemotherapy. KLK4 protein is localized in the cytoplasm of tumor and stroma cells. In this patient cohort, elevated stroma cell KLK4 expression, but not tumor cell KLK4 expression, is predictive for poor disease-free survival by univariate analysis (hazard ratio: 2.26, p=0.001) and multivariable analysis (hazard ratio: 2.12, p<0.01). Likewise, univariate analysis revealed a trend for statistical significance of elevated KLK4 stroma cell expression for overall survival of TNBC patients as well.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Klk4 ; Biomarker ; Immunohistochemistry ; Kallikrein-related Peptidase ; Predictive ; Triple-negative Breast Cancer; Plasminogen-activator; Prostate-cancer; Precision Medicine; Targeted Therapies; Clinical-relevance; Biological-fluids; American Society; Serine Proteases; Messenger-rna; Expression
ISSN (print) / ISBN
1431-6730
e-ISSN
1437-4315
Journal
Biological Chemistry
Quellenangaben
Volume: 398,
Issue: 10,
Pages: 1151-1164
Publisher
de Gruyter
Publishing Place
Berlin
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Analytical Pathology (AAP)