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

BMC Cancer

Research Article

Maria Tengström¹  Vesa Kataja¹  Veli-Matti Kosma²  Arto Mannermaa²  Bozena Berdel²  Mikko Pelkonen²  Kaisa Luostari²  Ylermi Soini²  Hermanni Ahonen² 

[1] Institute of Clinical Medicine, Oncology, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland;Cancer Center, Kuopio University Hospital, P.O. Box 1777, FI-70211, Kuopio, Finland;Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland;Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland;Imaging Center, Clinical Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211, Kuopio, Finland;

关键词: Biomarkers;    Breast cancer;    Extracellular matrix;    Gene expression profiling;    Hepsin;    Membrane-associated proteins;    Prognosis;    TMPRSS1;    Type II transmembrane serine proteases;    TMPRSS3;   

DOI  :  10.1186/s12885-015-1440-5

 received in 2014-11-15, accepted in 2015-05-15,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundHepsin, (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.MethodsImmunohistochemical 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.ResultsLow 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.ConclusionsThe 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.

【 授权许可】

Unknown   
© Pelkonen et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.