Skip to main content
Top
Published in: Medical Oncology 2/2013

01-06-2013 | Original Paper

Prognostic value of TMPRSS4 expression in patients with breast cancer

Authors: Bin Liang, Mingzhe Wu, Yuehua Bu, Ainong Zhao, Fang Xie

Published in: Medical Oncology | Issue 2/2013

Login to get access

Abstract

Transmembrane protease, serine 4 (TMPRSS4), is a novel type II transmembrane serine protease that is highly expressed on the cell surface in pancreatic, thyroid, lung, and other cancer tissues, although its oncogenic significance and molecular mechanisms are unknown. In a series of 109 primary breast cancer patients, we performed a comprehensive analysis of TMPRSS4 expression using immunohistochemistry. The relationship between TMPRSS4 expression and the clinicopathological characteristics or prognosis was evaluated. Results showed that breast cancer tissues exhibited higher levels of TMPRSS4 expression compared with benign tissues (65.1 versus 17.5 %, P < 0.001). High expression of TMPRSS4 was significantly correlated with lymph node metastasis (P < 0.001), high pathological grade (P = 0.001), and tumor size >2 cm (P = 0.006), but not correlated with other clinicopathological parameters, including the patient’s age (P = 0.289), menopausal status (P = 0.300), histological subtype (P = 0.418), and status of estrogen receptor (ER) (P = 0.913), progesterone receptor (PR) (P = 0.247), and HER-2 (P = 0.882). Patients with high expression of TMPRSS4 had shorter OS and DFS than those with low expression (P = 0.0009 and P = 0.0044, respectively). TMPRSS4 expression and lymph node metastasis were independent prognostic factors for both OS and DFS by multivariate analysis. Based on our results, we propose TMPRSS4 as a putative biological marker for breast cancer and as an indicator of poor prognosis.
Literature
1.
go back to reference Jemal A, Bray F, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef Jemal A, Bray F, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef
2.
go back to reference Wei G, Wang Y, Zhang P, Lu J, Mao JH. Evaluating the prognostic significance of FBXW7 expression level in human breast cancer by a meta-analysis of transcriptional profiles. J cancer sci ther. 2012;4(9):299–305.PubMedCrossRef Wei G, Wang Y, Zhang P, Lu J, Mao JH. Evaluating the prognostic significance of FBXW7 expression level in human breast cancer by a meta-analysis of transcriptional profiles. J cancer sci ther. 2012;4(9):299–305.PubMedCrossRef
3.
go back to reference Dechaphunkul A, Phukaoloun M, Kanjanapradit K, Graham K, Ghosh S, Santos C, et al. Prognostic significance of tissue inhibitor of metalloproteinase-1 in breast cancer. Int J breast cancer;2012:290854.PubMed Dechaphunkul A, Phukaoloun M, Kanjanapradit K, Graham K, Ghosh S, Santos C, et al. Prognostic significance of tissue inhibitor of metalloproteinase-1 in breast cancer. Int J breast cancer;2012:290854.PubMed
4.
go back to reference Netzel-Arnett S, Hooper JD, Szabo R, Madison EL, Quigley JP, Bugge TH, et al. Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer metastasis rev. 2003;22(2–3):237–58.PubMedCrossRef Netzel-Arnett S, Hooper JD, Szabo R, Madison EL, Quigley JP, Bugge TH, et al. Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer metastasis rev. 2003;22(2–3):237–58.PubMedCrossRef
5.
go back to reference Wallrapp C, Hahnel S, Muller-Pillasch F, Burghardt B, Iwamura T, Ruthenburger M, et al. A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. Cancer Res. 2000;60(10):2602–6.PubMed Wallrapp C, Hahnel S, Muller-Pillasch F, Burghardt B, Iwamura T, Ruthenburger M, et al. A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. Cancer Res. 2000;60(10):2602–6.PubMed
6.
go back to reference Kebebew E, Peng M, Reiff E, Duh QY, Clark OH, McMillan A. ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. Ann Surg. 2005;242(3):353–61. discussion 61–3.PubMed Kebebew E, Peng M, Reiff E, Duh QY, Clark OH, McMillan A. ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. Ann Surg. 2005;242(3):353–61. discussion 61–3.PubMed
7.
go back to reference Jung H, Lee KP, Park SJ, Park JH, Jang YS, Choi SY, et al. TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition. Oncogene. 2008;27(18):2635–47.PubMedCrossRef Jung H, Lee KP, Park SJ, Park JH, Jang YS, Choi SY, et al. TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition. Oncogene. 2008;27(18):2635–47.PubMedCrossRef
8.
go back to reference Kim S, Kang HY, Nam EH, Choi MS, Zhao XF, Hong CS, et al. TMPRSS4 induces invasion and epithelial-mesenchymal transition through upregulation of integrin alpha5 and its signaling pathways. Carcinogenesis. 2010;31(4):597–606.PubMedCrossRef Kim S, Kang HY, Nam EH, Choi MS, Zhao XF, Hong CS, et al. TMPRSS4 induces invasion and epithelial-mesenchymal transition through upregulation of integrin alpha5 and its signaling pathways. Carcinogenesis. 2010;31(4):597–606.PubMedCrossRef
9.
go back to reference Larzabal L, Nguewa PA, Pio R, Blanco D, Sanchez B, Rodriguez MJ, et al. Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology. Br J Cancer. 2011;105(10):1608–14.PubMedCrossRef Larzabal L, Nguewa PA, Pio R, Blanco D, Sanchez B, Rodriguez MJ, et al. Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology. Br J Cancer. 2011;105(10):1608–14.PubMedCrossRef
10.
go back to reference Li T, Zeng ZC, Wang L, Qiu SJ, Zhou JW, Zhi XT, et al. Radiation enhances long-term metastasis potential of residual hepatocellular carcinoma in nude mice through TMPRSS4-induced epithelial-mesenchymal transition. Cancer Gene Ther. 2011;18(9):617–26.PubMedCrossRef Li T, Zeng ZC, Wang L, Qiu SJ, Zhou JW, Zhi XT, et al. Radiation enhances long-term metastasis potential of residual hepatocellular carcinoma in nude mice through TMPRSS4-induced epithelial-mesenchymal transition. Cancer Gene Ther. 2011;18(9):617–26.PubMedCrossRef
11.
go back to reference Grutzmann R, Pilarsky C, Ammerpohl O, Luttges J, Bohme A, Sipos B, et al. Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays. Neoplasia. 2004;6(5):611–22.PubMedCrossRef Grutzmann R, Pilarsky C, Ammerpohl O, Luttges J, Bohme A, Sipos B, et al. Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays. Neoplasia. 2004;6(5):611–22.PubMedCrossRef
12.
go back to reference Iacobuzio-Donahue CA, Ashfaq R, Maitra A, Adsay NV, Shen-Ong GL, Berg K, et al. Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies. Cancer Res. 2003;63(24):8614–22.PubMed Iacobuzio-Donahue CA, Ashfaq R, Maitra A, Adsay NV, Shen-Ong GL, Berg K, et al. Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies. Cancer Res. 2003;63(24):8614–22.PubMed
13.
go back to reference Ma XJ, Patel R, Wang X, Salunga R, Murage J, Desai R, et al. Molecular classification of human cancers using a 92-gene real-time quantitative polymerase chain reaction assay. Arch Pathol Lab Med. 2006;130(4):465–73.PubMed Ma XJ, Patel R, Wang X, Salunga R, Murage J, Desai R, et al. Molecular classification of human cancers using a 92-gene real-time quantitative polymerase chain reaction assay. Arch Pathol Lab Med. 2006;130(4):465–73.PubMed
14.
go back to reference Bener A, Ayub H, Kakil R, Ibrahim W. Patterns of cancer incidence among the population of Qatar: a worldwide comparative study. Asian Pac J Cancer Prev: APJCP. 2008;9(1):19–24.PubMed Bener A, Ayub H, Kakil R, Ibrahim W. Patterns of cancer incidence among the population of Qatar: a worldwide comparative study. Asian Pac J Cancer Prev: APJCP. 2008;9(1):19–24.PubMed
15.
go back to reference Bener A, El Ayoubi HR, Basha B, Joseph S, Chouchane L. Breast cancer screening barriers: knowledge, attitudes and practices of women toward breast cancer. Breast J. 2011;17(1):115–6.PubMedCrossRef Bener A, El Ayoubi HR, Basha B, Joseph S, Chouchane L. Breast cancer screening barriers: knowledge, attitudes and practices of women toward breast cancer. Breast J. 2011;17(1):115–6.PubMedCrossRef
16.
go back to reference Huang CS, Chang KJ, Shen CY. Breast cancer screening in Taiwan and China. Breast dis. 2001;13:41–8.PubMed Huang CS, Chang KJ, Shen CY. Breast cancer screening in Taiwan and China. Breast dis. 2001;13:41–8.PubMed
17.
go back to reference Weigel MT, Dowsett M. Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocr Relat Cancer. 2010;17(4):R245–62.PubMedCrossRef Weigel MT, Dowsett M. Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocr Relat Cancer. 2010;17(4):R245–62.PubMedCrossRef
18.
go back to reference Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–42.PubMedCrossRef Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–42.PubMedCrossRef
19.
go back to reference Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14(6):818–29.PubMedCrossRef Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14(6):818–29.PubMedCrossRef
Metadata
Title
Prognostic value of TMPRSS4 expression in patients with breast cancer
Authors
Bin Liang
Mingzhe Wu
Yuehua Bu
Ainong Zhao
Fang Xie
Publication date
01-06-2013
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2013
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0497-8

Other articles of this Issue 2/2013

Medical Oncology 2/2013 Go to the issue