Skip to main content

Advertisement

SpringerLink
Log in

TFF3 and HER2 expression and their correlation with survival in gastric cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

The molecular biomarkers human epidermal growth factor receptor-2 (HER2) and trefoil factor 3 (TFF3) are reported to play important roles in the pathogenesis of gastric cancer (GC). In this study, we investigated the clinicopathological and prognostic significance of TFF3 and HER2 expression in GC and explored the correlation between these two biomarkers. Ninety-two patients who were diagnosed with GC were enrolled. TFF3 and HER2 expression was determined on tumor tissues. The results showed that TFF3 and HER2 were positively expressed in 42.7 and 10.9 % of the cases, respectively. There were significantly higher rates of TFF3 positivity in patients with deep invasive tumors and advanced stage ones. Patients with negative TFF3 staining survived longer than those with the presence of TFF3, with 5-year overall survival (OS) rates of 57.1 ± 7.1 and 39.5 ± 7.5 %, respectively (P = 0.033). However, HER2 positivity was not significantly associated with OS (P = 0.262). Multivariate analysis demonstrated TFF3 expression to be an independent indicator for short-term survival, with a hazard ratio of 2.327 (95 % confidence interval (CI), 1.202–4.507, P = 0.012). There was a trend that the expression of TFF3 was more frequent in HER2 negative tumors than in HER2 positive ones (positive rates: 16.3 vs. 4.7 %, P = 0.098). Patients with HER2-negative/TFF3-negative GC presented higher OS than those with other phenotypes (P = 0.009). This study suggests that TFF3 is an independent indicator for survival in GC, while HER2 is not associated with the outcome. Patients with HER2-negative/TFF3-negative GC have the best outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–50.

    Article  PubMed  Google Scholar 

  2. Gonzalez CA, Agudo A. Carcinogenesis, prevention and early detection of gastric cancer: where we are and where we should go. Int J Cancer. 2012;130:745–53.

    Article  CAS  PubMed  Google Scholar 

  3. Chua TC, Merrett ND. Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes–a systematic review. Int J Cancer. 2012;130:2845–56.

    Article  CAS  PubMed  Google Scholar 

  4. Gu J, Zheng L, Wang Y, et al. Prognostic significance of HER2 expression based on trastuzumab for gastric cancer (ToGA) criteria in gastric cancer: an updated meta-analysis. Tumour Biol. 2014;35:5315–21.

    Article  CAS  PubMed  Google Scholar 

  5. Hoffmann W. Trefoil factors TFF (trefoil factor family) peptide-triggered signals promoting mucosal restitution. Cell Mol Life Sci. 2005;62:2932–8.

    Article  CAS  PubMed  Google Scholar 

  6. Hoffmann W, Jagla W, Wiede A. Molecular medicine of TFF-peptides: from gut to brain. Histol Histopathol. 2001;16:319–34.

    CAS  PubMed  Google Scholar 

  7. John R, El-Rouby NM, Tomasetto C, et al. Expression of TFF3 during multistep colon carcinogenesis. Histol Histopathol. 2007;22:743–51.

    CAS  PubMed  Google Scholar 

  8. Dhar DK, Wang TC, Tabara H, et al. Expression of trefoil factor family members correlates with patient prognosis and neoangiogenesis. Clin Cancer Res. 2005;11:6472–8.

    Article  CAS  PubMed  Google Scholar 

  9. Meng JR, Tang HZ, Zhou KZ, et al. TFF3 and survivin expressions associate with a lower survival rate in gastric cancer. Clin Exp Med. 2013;13:297–303.

    Article  CAS  PubMed  Google Scholar 

  10. Ding A, Zhao W, Shi X, et al. Impact of NPM, TFF3 and TACC1 on the prognosis of patients with primary gastric cancer. PLoS One. 2013;8:e82136.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Xu CC, Yue L, Wei HJ, et al. Significance of TFF3 protein and Her-2/neu status in patients with gastric adenocarcinoma. Pathol Res Pract. 2013;209:479–85.

    Article  CAS  PubMed  Google Scholar 

  12. Lauwers GY, Carneiro F, Graham DY. Gastric carcinoma. In: Bowman FT, Carneiro F, Hruban RH, editors. Classification of tumours of the digestive system. Lyon: IARC; 2010.

    Google Scholar 

  13. Sobin LH, Gospodarowicz MK, Wittekind C, editors. TNM classification of malignant tumours. Chichester: Wiley; 2010.

    Google Scholar 

  14. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.

    Article  CAS  PubMed  Google Scholar 

  15. Muskett FW, May FE, Westley BR, et al. Solution structure of the disulfide-linked dimer of human intestinal trefoil factor (TFF3): the intermolecular orientation and interactions are markedly different from those of other dimeric trefoil proteins. Biochemistry. 2003;42:15139–47.

    Article  CAS  PubMed  Google Scholar 

  16. Suemori S, Lynch-Devaney K, Podolsky DK. Identification and characterization of rat intestinal trefoil factor: tissue- and cell-specific member of the trefoil protein family. Proc Natl Acad Sci U S A. 1991;88:11017–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Podolsky DK, Lynch-Devaney K, Stow JL, et al. Identification of human intestinal trefoil factor Goblet cell-specific expression of a peptide targeted for apical secretion. J Biol Chem. 1993;268:12230.

    CAS  PubMed  Google Scholar 

  18. Dignass A, Lynch-Devaney K, Kindon H, et al. Trefoil peptides promote epithelial migration through a transforming growth factor beta-independent pathway. J Clin Invest. 1994;94:376–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Xian CJ, Howarth GS, Mardell CE, et al. Temporal changes in TFF3 expression and jejunal morphology during methotrexate-induced damage and repair. Am J Physiol. 1999;277:G785–95.

    CAS  PubMed  Google Scholar 

  20. Efstathiou JA, Noda M, Rowan A, et al. Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells. Proc Natl Acad Sci U S A. 1998;95:3122–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Emami S, Le Floch N, Bruyneel E, et al. Induction of scattering and cellular invasion by trefoil peptides in src- and RhoA-transformed kidney and colonic epithelial cells. FASEB J. 2001;15:351–61.

    Article  CAS  PubMed  Google Scholar 

  22. Ahmed AR, Griffiths AB, Tilby MT, et al. TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease. Am J Pathol. 2012;180:904–16.

    Article  PubMed  Google Scholar 

  23. Leung WK, Yu J, Chan FK, et al. Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas, intestinal metaplasia, and non-neoplastic gastric tissues. J Pathol. 2002;197:582–8.

    Article  CAS  PubMed  Google Scholar 

  24. Huang Z, Zhang X, Lu H, et al. Serum trefoil factor 3 is a promising non-invasive biomarker for gastric cancer screening: a monocentric cohort study in China. BMC Gastroenterol. 2014;14:74.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Deng J, Zhang R, Pan Y, et al. N stages of the seventh edition of TNM Classification are the most intensive variables for predictions of the overall survival of gastric cancer patients who underwent limited lymphadenectomy. Tumour Biol. 2014;35:3269–81.

    Article  CAS  PubMed  Google Scholar 

  26. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–12.

    Article  CAS  PubMed  Google Scholar 

  27. Scholl S, Beuzeboc P, Pouillart P. Targeting HER2 in other tumor types. Ann Oncol. 2001;12 Suppl 1:S81–7.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China

    Jianchun Gu, Leizhen Zheng, Li Zhang, Siyu Chen, Meiling Zhu & Xiaoping Li

  2. Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

    Jianchun Gu & Yajie Wang

Authors
  1. Jianchun Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leizhen Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Siyu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Meiling Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoping Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yajie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yajie Wang.

Additional information

Jianchun Gu and Leizhen Zheng contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gu, J., Zheng, L., Zhang, L. et al. TFF3 and HER2 expression and their correlation with survival in gastric cancer. Tumor Biol. 36, 3001–3007 (2015). https://doi.org/10.1007/s13277-014-2933-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2933-6

Keywords

Search

Navigation