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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Low expression levels of hepsin and TMPRSS3 are associated with poor breast cancer survival

Authors: Mikko Pelkonen, Kaisa Luostari, Maria Tengström, Hermanni Ahonen, Bozena Berdel, Vesa Kataja, Ylermi Soini, Veli-Matti Kosma, Arto Mannermaa

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Hepsin, (also called TMPRSS1) and TMPRSS3 are type II transmembrane serine proteases (TTSPs) that are involved in cancer progression. TTSPs can remodel extracellular matrix (ECM) and, when dysregulated, promote tumor progression and metastasis by inducing defects in basement membrane and ECM molecules. This study investigated whether the gene and protein expression levels of these TTSPs were associated with breast cancer characteristics or survival.

Methods

Immunohistochemical staining was used to evaluate hepsin levels in 372 breast cancer samples and TMPRSS3 levels in 373 samples. TMPRSS1 mRNA expression was determined in 125 invasive and 16 benign breast tumor samples, and TMPRSS3 mRNA expression was determined in 167 invasive and 23 benign breast tumor samples. The gene and protein expression levels were analyzed for associations with breast cancer-specific survival and clinicopathological parameters.

Results

Low TMPRSS1 and TMPRSS3 mRNA expression levels were independent prognostic factors for poor breast cancer survival during the 20-year follow-up (TMPRSS1, P = 0.023; HR, 2.065; 95 % CI, 1.106–3.856; TMPRSS3, P = 0.013; HR, 2.106; 95 % CI, 1.167–3.800). Low expression of the two genes at the mRNA and protein levels associated with poorer survival compared to high levels (log rank P-values 0.015–0.042). Low TMPRSS1 mRNA expression was also an independent marker of poor breast cancer prognosis in patients treated with radiotherapy (P = 0.034; HR, 2.344; 95 % CI, 1.065–5.160). Grade III tumors, large tumor size, and metastasis were associated with low mRNA and protein expression levels.

Conclusions

The results suggest that the TTSPs hepsin and TMPRSS3 may have similar biological functions in the molecular pathology of breast cancer. Low mRNA and protein expression levels of the studied TTSPs were prognostic markers of poor survival in breast cancer.
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Metadata
Title
Low expression levels of hepsin and TMPRSS3 are associated with poor breast cancer survival
Authors
Mikko Pelkonen
Kaisa Luostari
Maria Tengström
Hermanni Ahonen
Bozena Berdel
Vesa Kataja
Ylermi Soini
Veli-Matti Kosma
Arto Mannermaa
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1440-5

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