Skip to main content
Top
Published in: Tumor Biology 6/2014

01-06-2014 | Research Article

Clinical implication of TMPRSS4 expression in human gallbladder cancer

Authors: Xiao-Yang Wu, Li Zhang, Ke-Ming Zhang, Ming-Hua Zhang, Ting-Yan Ruan, Chao-Ying Liu, Jun-Ying Xu

Published in: Tumor Biology | Issue 6/2014

Login to get access

Abstract

Altered expression of transmembrane protease/serine 4 (TMPRSS4) is observed in various types of human cancers. However, the clinical significance of TMPRSS4 expression in gallbladder cancer (GBC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of TMPRSS4 in GBC. The levels of TMPRSS4 mRNA and protein in GBC tissues and adjacent noncancerous tissues were evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry. To investigate the correlations between TMPRSS4 and the clinicopathological features of GBC, the expression of TMPRSS4 in 97 patients with GBC were detected by immunohistochemistry. The correlation of TMPRSS4 expression with patients’ survival rate was assessed by Kaplan–Meier and Cox regression. Our results showed that the expression levels of TMPRSS4 mRNA and protein in GBC tissues were both significantly higher than those in adjacent noncancerous tissues. Immunohistochemical staining revealed that high TMPRSS4 expression was closely correlated with tumor size (P = 0.032), histological grade (P = 0.002), pathologic T stage (P = 0.005), clinical stage (P = 0.013), and lymph node metastasis (P = 0.003). Moreover, the results of Kaplan–Meier analysis indicated that a high expression level of TMPRSS4 resulted in a significantly poor prognosis of GBC patients. Multivariate analysis showed that the status of TMPRSS4 expression was an independent prognostic factor for GBC patients. Our results showed that TMPRSS4 plays a key role in GBC and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in GBC.
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106–30.CrossRefPubMed Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106–30.CrossRefPubMed
3.
go back to reference Balachandran P, Agarwal S, Krishnani N, Pandey CM, Kumar A, Sikora SS, et al. Predictors of long-term survival in patients with gallbladder cancer. J Gastrointest Surg. 2006;10:848–54.CrossRefPubMed Balachandran P, Agarwal S, Krishnani N, Pandey CM, Kumar A, Sikora SS, et al. Predictors of long-term survival in patients with gallbladder cancer. J Gastrointest Surg. 2006;10:848–54.CrossRefPubMed
4.
go back to reference Kim WS, Choi DW, You DD, Ho CY, Heo JS, Choi SH. Risk factors influencing recurrence, patterns of recurrence, and the efficacy of adjuvant therapy after radical resection for gallbladder carcinoma. J Gastrointest Surg. 2010;14:679–87. doi:10.1007/s11605-009-1140-z.CrossRefPubMed Kim WS, Choi DW, You DD, Ho CY, Heo JS, Choi SH. Risk factors influencing recurrence, patterns of recurrence, and the efficacy of adjuvant therapy after radical resection for gallbladder carcinoma. J Gastrointest Surg. 2010;14:679–87. doi:10.​1007/​s11605-009-1140-z.CrossRefPubMed
6.
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;22:237–58.CrossRefPubMed 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;22:237–58.CrossRefPubMed
7.
go back to reference Szabo R, Wu Q, Dickson RB, Netzel-Arnett S, Antalis TM, Bugge TH. Type II transmembrane serine proteases. Thromb Haemost. 2003;90:185–93.PubMed Szabo R, Wu Q, Dickson RB, Netzel-Arnett S, Antalis TM, Bugge TH. Type II transmembrane serine proteases. Thromb Haemost. 2003;90:185–93.PubMed
8.
go back to reference Webb SL, Sanders AJ, Mason MD, Jiang WG. Type II transmembrane serine protease (TTSP) deregulation in cancer. Front Biosci (Landmark Ed). 2011;16:539–52.CrossRef Webb SL, Sanders AJ, Mason MD, Jiang WG. Type II transmembrane serine protease (TTSP) deregulation in cancer. Front Biosci (Landmark Ed). 2011;16:539–52.CrossRef
9.
go back to reference Wallrapp C, Hähnel S, Müller-Pillasch F, Burghardt B, Iwamura T, Ruthenbürger M, et al. A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. Cancer Res. 2000;60:2602–6.PubMed Wallrapp C, Hähnel S, Müller-Pillasch F, Burghardt B, Iwamura T, Ruthenbürger M, et al. A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. Cancer Res. 2000;60:2602–6.PubMed
12.
17.
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;31:597–606. doi:10.1093/carcin/bgq024.CrossRefPubMed 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;31:597–606. doi:10.​1093/​carcin/​bgq024.CrossRefPubMed
18.
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;27:2635–47. doi:10.1038/sj.onc.1210914.CrossRefPubMed 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;27:2635–47. doi:10.​1038/​sj.​onc.​1210914.CrossRefPubMed
19.
go back to reference 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;69:1828–35. doi:10.1158/0008-5472.CAN-08-3728.CrossRefPubMed 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;69:1828–35. doi:10.​1158/​0008-5472.​CAN-08-3728.CrossRefPubMed
20.
go back to reference 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;29:861–72. doi:10.1007/s10637-010-9435-1.CrossRefPubMed 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;29:861–72. doi:10.​1007/​s10637-010-9435-1.CrossRefPubMed
Metadata
Title
Clinical implication of TMPRSS4 expression in human gallbladder cancer
Authors
Xiao-Yang Wu
Li Zhang
Ke-Ming Zhang
Ming-Hua Zhang
Ting-Yan Ruan
Chao-Ying Liu
Jun-Ying Xu
Publication date
01-06-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-1716-4

Other articles of this Issue 6/2014

Tumor Biology 6/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine