Abstracts
Transmembrane protease/serine 4 (TMPRSS4), a member of the type II transmembrane serine protease family, is highly expressed in some human cancers and involved in the EMT regulation of cancer cells. The prognostic value of TMPRSS4 in colorectal cancer (CRC) has not been discussed. This study aims to evaluate the association between TMPRSS4 expressions and survival in CRC patients. Immunohistochemistry revealed high expression of TMPRSS4 in 69/122 CRC samples, compared with 14/47 in normal tissues (P < 0.01). Correlation analysis showed high expression of TMPRSS4 was significantly associated with advanced TNM stage (P = 0.011), pT (P = 0.019), pN (P = 0.035), and pM status (P = 0.004). Higher TMPRSS4 predicted shorter overall survival (OS) and disease-free survival (DFS) in CRC patients (P < 0.01, both). Moreover, both TMPRSS4 expression and TNM stage were independent predictive factors of OS and DFS in Cox regression analysis. The findings in our study demonstrated the potential value of TMPRSS4 expression level as a prognostic biomarker for CRC patients.
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Choi SY, Bertram S, Glowacka I, Park YW, Pohlmann S. Type II transmembrane serine proteases in cancer and viral infections. Trends Mol Med. 2009;15(7):303–12.
Szabo R, Bugge TH. Type II transmembrane serine proteases in development and disease. Int J Biochem Cell Biol. 2008;40(6–7):1297–316.
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.
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.
Nguyen TH, Weber W, Havari E, Connors T, Bagley RG, McLaren R, et al. Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia. Int J Oncol. 2012;41(3):829–38.
Jarzab B, Wiench M, Fujarewicz K, Simek K, Jarzab M, Oczko-Wojciechowska M, et al. Gene expression profile of papillary thyroid cancer sources of variability and diagnostic implications. Cancer Res. 2005;65(4):1587–97.
Kebebew E, Peng M, Reiff E, Duh Q-Y, Clark OH, McMillan A. ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. Trans Meet Am Surg Assoc. 2005;123:57–66.
Kebebew E, Peng M, Reiff E, McMillan A. Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer. 2006;106(12):2592–7.
Cheng D, Kong H, Li Y. TMPRSS4 as a poor prognostic factor for triple-negative breast cancer. Int J Mol Sci. 2013;14(7):14659–68.
Liang B, Wu M, Bu Y, Zhao A, Xie F. Prognostic value of TMPRSS4 expression in patients with breast cancer. Med Oncol. 2013;30(2):497.
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.
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.
Cheng H, Fukushima T, Takahashi N, Tanaka H, Kataoka H. Hepatocyte growth factor activator inhibitor type 1 regulates epithelial to mesenchymal transition through membrane-bound serine proteinases. Cancer Res. 2009;69(5):1828–35.
Jia JB, Wang WQ, Sun HC, Liu L, Zhu XD, Kong LQ, et al. A novel tripeptide, tyroserleutide, inhibits irradiation-induced invasiveness and metastasis of hepatocellular carcinoma in nude mice. Invest New Drugs. 2011;29(5):861–72.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.
Bolocan A, Ion D, Ciocan DN, Paduraru DN. Prognostic and predictive factors in colorectal cancer. Chirurgia (Bucur). 2012;107(5):555–63.
Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420–8.
Zeisberg M, Neilson EG. Biomarkers for epithelial-mesenchymal transitions. J Clin Invest. 2009;119(6):1429–37.
Tiwari N, Gheldof A, Tatari M, Christofori G. EMT as the ultimate survival mechanism of cancer cells. Semin Cancer Biol. 2012;22(3):194–207.
Scheel C, Weinberg RA. Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Semin Cancer Biol. 2012;22(5–6):396–403.
Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–15.
Guo W, Keckesova Z, Donaher JL, Shibue T, Tischler V, Reinhardt F, et al. Slug and Sox9 cooperatively determine the mammary stem cell state. Cell. 2012;148(5):1015–28.
Sampieri K, Fodde R. Cancer stem cells and metastasis. Semin Cancer Biol. 2012;22(3):187–93.
Zhu Q-C, Gao R-Y, Wu W, Qin H-L. Epithelial-mesenchymal transition and its role in the pathogenesis of colorectal cancer. Asian Pac J Cancer Prev. 2013;14(5):2689–98.
Ohler A, Becker-Pauly C. Morpholino knockdown of the ubiquitously expressed transmembrane serine protease TMPRSS4a in zebrafish embryos exhibits severe defects in organogenesis and cell adhesion. Biol Chem. 2011;392(7):653–64.
Choi SY, Shin HC, Kim SY, Park YW. Role of TMPRSS4 during cancer progression. Drug News Perspect. 2008;21(8):417–23.
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Houmin Zhou is a co-first author
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Huang, A., Zhou, H., Zhao, H. et al. High expression level of TMPRSS4 predicts adverse outcomes of colorectal cancer patients. Med Oncol 30, 712 (2013). https://doi.org/10.1007/s12032-013-0712-7
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DOI: https://doi.org/10.1007/s12032-013-0712-7