Annals of Surgical Oncology

, 15:2606 | Cite as

Prognostic Relevance of Tensin4 Expression in Human Gastric Cancer

  • Katsuya Sakashita
  • Koshi Mimori
  • Fumiaki Tanaka
  • Yukio Kamohara
  • Hiroshi Inoue
  • Tetsuji Sawada
  • Kosei Hirakawa
  • Masaki Mori
Laboratory Research

Abstract

Background

The Tensin4 gene is involved in various biological events by mediating signal transduction. This study was designed to clarify its clinical significance in gastric cancer.

Methods

A total of 114 gastric cancer patients were enrolled in this study, and we obtained paired samples from tumor tissue and matched normal mucosa. Total RNA was extracted, and TNS4 mRNA expression was quantified using real-time reverse-transcription polymerase chain reaction. TNS4 protein expression was investigated by immunohistochemistry. Additionally, the relationship between TNS4 expression and clinicopathologic factors was statistically analyzed.

Results

TNS4 mRNA expression was significantly higher in tumor tissue than in normal mucosa (p < 0.0001). Additional immunohistochemical analysis demonstrated that TNS4 protein was predominantly expressed in gastric cancer. Tumors with higher TNS4 mRNA expression showed histologically poorer grade (p < 0.02), deeper invasion into the serosa (p < 0.01), more positive lymph node metastasis (p < 0.02) or peritoneal dissemination (p < 0.05). Patients with high TNS4 mRNA expression tumor were more likely to have cancer-related death (p < 0.05). A Kaplan–Meier curve also demonstrated that patients with high TNS4 expression tumor had significantly poorer prognosis (p < 0.01) than those with low TNS4 expression tumor. In particular, the 2-year overall survival rates were 48.2% and 83.1%, respectively, a very significant difference. Multivariate analysis revealed that high TNS4 mRNA expression was an independent prognostic predictor (relative risk 1.41, 95% confidence interval 1.03–1.96, p = 0.03).

Conclusion

TNS4 was frequently overexpressed in gastric cancer, and tumors with high TNS4 mRNA expression showed biologically aggressive behavior. High TNS4 mRNA expression may be a novel prognostic predictor for those patients.

Keywords

TNS4 Gastric cancer Prognostic predictor 

References

  1. 1.
    Alberts SR, Cervantes A, van de Velde CJ. Gastric cancer: epidemiology, pathology and treatment. Ann Oncol 2003; 14:31–6Google Scholar
  2. 2.
    Roder DM. The epidemiology of gastric cancer. Gastric Cancer 2002; 5:5–11PubMedCrossRefGoogle Scholar
  3. 3.
    Jemal A, Tiwari RC, Murray T, et al. Cancer Statistics, 2004. CA Cancer J Clin 2004; 54:8–29PubMedCrossRefGoogle Scholar
  4. 4.
    Agochiya M, Brunton VG, Owens DW, et al. Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene 1999; 18:5646–53PubMedCrossRefGoogle Scholar
  5. 5.
    Chen H, Ishii A, Wong WK, et al. Molecular characterization of human tensin. Biochem J 2000; 351:403–11PubMedCrossRefGoogle Scholar
  6. 6.
    Zhou MM, Ravichandran KS, Olejniczak EF, et al. Structure and ligand recognition of the phosphotyrosine binding domain of Shc. Nature 1995; 378:584–92PubMedCrossRefGoogle Scholar
  7. 7.
    Davis S, Lu ML, Lo SH, et al. Presence of an SH2 domain in the actin-binding protein tensin. Science 1991; 252:712–5PubMedCrossRefGoogle Scholar
  8. 8.
    Lo SH, Weisberg E, Chen LB. Tensin: A potential link between the cytoskeleton and signal transduction. Bioessays 1994; 16:817–23PubMedCrossRefGoogle Scholar
  9. 9.
    Tice DA, Biscardi JS, Nickles AL, et al. Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. Proc Natl Acad Sci USA 1999; 96:1415–20PubMedCrossRefGoogle Scholar
  10. 10.
    Lo SH, An Q, Bao S, et al. Molecular cloning of chick cardiac muscle tensin. Full-length cDNA sequence, expression and characterization. J Biol Chem 1994; 269:22310–9PubMedGoogle Scholar
  11. 11.
    Kook S, Kim DH, Shim SR, et al. Caspase-dependent cleavage of tensin induces disruption of actin cytoskeleton during apoptosis. Biochem Biophys Res Commun 2003; 303:37–45PubMedCrossRefGoogle Scholar
  12. 12.
    Cui Y, Liao Y, Lo SH. Epidermal growth factor modurates Tyrosine phosphorylation of a novel tensin family member, tensin3. Mol Cancer Res 2004; 2:225–32PubMedGoogle Scholar
  13. 13.
    Bockholt SM, Burridge K. Cell spreading on extracellular matrix proteins induces tyrosine phosphorylation of tensin. J Biol Chem 1993; 268:14565–7PubMedGoogle Scholar
  14. 14.
    Auger KR, Songyang Z, Lo SH, et al. Platelet-derived growth factor-induced formation of tensin and phosphoinositide 3-kinase complexes. J Biol Chem 1996; 271:23452–7PubMedCrossRefGoogle Scholar
  15. 15.
    Lo S, Lo S., Huey Lo SH. Cleavage of cten by caspase-3 during apoptosis. Oncogene 2005; 24:4311–4PubMedCrossRefGoogle Scholar
  16. 16.
    Sasaki H, Moriyama S, Mizuno K, et al. Cten mRNA expression was correlated with tumor progression in lung cancers. Lung Cancer 2003; 40:151–5PubMedCrossRefGoogle Scholar
  17. 17.
    Sasaki H, Yukiue H, Kobayashi Y, et al. Cten mRNA expression is correlated with tumor progression in thymoma. Tumor Biol 2003; 24:271–4CrossRefGoogle Scholar
  18. 18.
    Lo SH, Lo TB. A COOH-terminal Tensin-like protein with prostate restricted expression, is down-regulated in prostate cancer. Cancer Res 2002; 62:4217–21PubMedGoogle Scholar
  19. 19.
    Liao YC, Si L, deVere White RW, et al. The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten regulates focal adhesion localization and growth suppression activity of DLC-1. J Cell Biol 2007; 176:43–9PubMedCrossRefGoogle Scholar
  20. 20.
    Mimori K, Mori M, Shiraishi T, et al. Clinical significance of tissue inhibitor of metalloproteinase expression in gastric carcinoma. Br J Cancer 1997; 76:531–6PubMedGoogle Scholar
  21. 21.
    Japanese Gastric Cancer Association: Japanese Classification of Gastric Cancer, 2nd English Edition. Gastric Cancer 1998; 1:10–24Google Scholar
  22. 22.
    Jass JR, Sobin LH, Watanabe H. The World Health Organization’s histologic classification of gastrointestinal tumors. A commentary on the second edition. Cancer 1990; 66:2162–7PubMedCrossRefGoogle Scholar
  23. 23.
    Ogawa K, Utsunomiya T, Mimori K, et al. Clinical significance human kallikrein gene 6 messenger RNA expression in colorectal cancer. Clin Cancer Res 2005; 11:2889–93PubMedCrossRefGoogle Scholar
  24. 24.
    Ohmachi T, Tanaka F, Mimori K, et al. Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res 2006; 12:3057–63PubMedCrossRefGoogle Scholar
  25. 25.
    Sasaki A, Iwashita Y, Shibata K, et al. Improved long-term survival after liver resection for hepatocellular carcinoma in the modern era: retrospective study from HCV-endemic areas. World J Surg 2006; 30:1567–78PubMedCrossRefGoogle Scholar
  26. 26.
    Ishii A, Lo SH. A role of tensin in skeletal muscle regeneration. Biochem J 2001; 356:734–45CrossRefGoogle Scholar
  27. 27.
    Chen H, Duncan IC, Bozorgchami H, et al. Tensin1 and a previously undocumented family member, tensin2, positively regulate cell migration. Proc Natl Acad Sci USA 2002; 99:733–8PubMedGoogle Scholar
  28. 28.
    Chen H, Lo SH. Regulation of tensin-promoted cell migration by its focal adhesion binding and Src homology domain 2. Biochem J 2003; 370:1039–45PubMedCrossRefGoogle Scholar
  29. 29.
    Yamashita M, Horikoshi S, Asanuma K, et al. Tensin is potentially involved in extracellular matrix production in mesangial cells. Histochem Cell Biol 2004; 121:245–54PubMedCrossRefGoogle Scholar
  30. 30.
    Liotta LA, Kohn EC. The microenvironment of the tumor-host interface. Nature 2001; 411:375–9PubMedCrossRefGoogle Scholar
  31. 31.
    Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer Staging, proximal disease, and the “different disease” hypothesis. Cancer 2000; 88:921–32PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2008

Authors and Affiliations

  • Katsuya Sakashita
    • 1
    • 2
  • Koshi Mimori
    • 1
  • Fumiaki Tanaka
    • 1
  • Yukio Kamohara
    • 1
  • Hiroshi Inoue
    • 1
  • Tetsuji Sawada
    • 2
  • Kosei Hirakawa
    • 2
  • Masaki Mori
    • 1
  1. 1.Department of Surgical Oncology, Medical Institute of BioregulationKyushu UniversityBeppuJapan
  2. 2.Department of Surgical OncologyOsaka City University Graduate School of MedicineAbeno-kuJapan

Personalised recommendations