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Upregulated ZO-1 correlates with favorable survival of gastrointestinal stromal tumor

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Abstract

Zonula occludens-1 (ZO-1) is a membrane-scaffolding protein that plays an important role in maintaining tight-junction integrity, which is disrupted in many invasive cancers and intestinal diseases. However, the expression of ZO-1 in gastrointestinal stromal tumor (GIST) and its relationship with clinical characteristics of this disease remain poorly understood. In this study, immunohistochemical analysis using tissue microarray was employed to evaluate the expression of ZO-1 in GIST and to investigate the relationship between its expression and GIST prognosis. High ZO-1 expression was displayed in 71.8 % of GIST patients, which was related to tumor diameter (p < 0.05). The Kaplan–Meier method and log-rank test indicated that high ZO-1 expression, small tumor diameter, tumor position in the esophagus, and a borderline-to-intermediate tumor grade displayed significant correlations with longer survival of GIST patients. The data suggest that ZO-1 expression is correlated with malignant phenotypes of GIST and it may serve as a favorable prognostic factor for GIST. These results also support a role for ZO-1 as a tumor-suppressor gene in GIST.

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References

  1. Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer. 2011;11:865–78.

    PubMed  CAS  Google Scholar 

  2. Agaimy A. Gastrointestinal stromal tumors (GIST) from risk strati-fication systems to the new TNM proposal: more questions than answers? A review emphasizing the need for a standardized GIST reporting. Int J Clin Exp Pathol. 2010;3:461–71.

    PubMed  Google Scholar 

  3. Liegl B, Hornick JL, Lazar AJ. Contemporary pathology of gastrointestinal stromal tumors. Hematol Oncol Clin North Am. 2009;23:49–68.

    Article  PubMed  Google Scholar 

  4. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33:459–65.

    Article  PubMed  Google Scholar 

  5. Machairiotis N, Kougioumtzi I, Zarogoulidis P, et al. Gastrointestinal stromal tumor mesenchymal neoplasms: the offspring that choose the wrong path. J Multidiscip Healthc. 2013;6:127–31.

    PubMed  Google Scholar 

  6. Kumar K, Rowsell C, Law C, et al. Coexistence of gastrointestinal stromal tumour and colorectal adenocarcinoma: two case reports. J Gastrointest Oncol. 2011;2:50–4.

    PubMed  Google Scholar 

  7. Roberts PJ, Eisenberg B. Clinical presentation of gastrointestinal stromal tumors and treatment of operable disease. Eur J Cancer. 2002;38(Suppl 5):S37–8.

    Article  PubMed  Google Scholar 

  8. Hassan I, You YN, Shyyan R, et al. Surgically managed gastrointestinal stromal tumors: a comparative and prognostic analysis. Ann Surg Oncol. 2008;15:52–9.

    Article  PubMed  Google Scholar 

  9. Tuveson DA, Willis NA, Jacks T, et al. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene. 2001;20:5054–8.

    Article  PubMed  CAS  Google Scholar 

  10. Mol CD, Dougan DR, Schneider TR, et al. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem. 2004;279:31655–63.

    Article  PubMed  CAS  Google Scholar 

  11. Rutkowski P, Debiec-Rychter M, Nowecki ZI, et al. Different factors are responsible for predicting relapses after primary tumors resection and for imatinib treatment outcomes in gastrointestinal stromal tumors. Med Sci Monit. 2007;13:CR515–22.

    Google Scholar 

  12. Rutkowski P, Nowecki ZI, Michej W, et al. Risk criteria and prognostic factors for predicting recurrences after resection of primary gastrointestinal stromal tumor. Ann Surg Oncol. 2007;14:2018–27.

    Article  PubMed  Google Scholar 

  13. Rutkowski P, Nowecki ZI, Debiec-Rychter M, et al. Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs). J Cancer Res Clin Oncol. 2007;133:589–97.

    Article  PubMed  CAS  Google Scholar 

  14. Chai Z, Goodenough DA, Paul DL. Cx50 requires an intact PDZ-binding motif and ZO-1 for the formation of functional intercellular channels. Mol Biol Cell. 2011;22:4503–12.

    Article  PubMed  CAS  Google Scholar 

  15. Giri S, Poindexter KM, Sundar SN, et al. Arecoline induced disruption of expression and localization of the tight junctional protein ZO-1 is dependent on the HER 2 expression in human endometrial Ishikawa cells. BMC Cell Biol. 2010;11:53.

    Article  PubMed  Google Scholar 

  16. Nemeth Z, Szasz AM, Somoracz A, et al. Zonula occludens-1, occludin, and E-cadherin protein expression in biliary tract cancers. Pathol Oncol Res. 2009;15:533–9.

    Article  PubMed  CAS  Google Scholar 

  17. Martin TA, Watkins G, Mansel RE, et al. Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer. Eur J Cancer. 2004;40:2717–25.

    Article  PubMed  CAS  Google Scholar 

  18. Resnick MB, Gavilanez M, Newton E, et al. Claudin expression in gastric adenocarcinomas: a tissue microarray study with prognostic correlation. Hum Pathol. 2005;36:886–92.

    Article  PubMed  CAS  Google Scholar 

  19. Smalley KS, Brafford P, Haass NK, et al. Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion. Am J Pathol. 2005;166:1541–54.

    Article  PubMed  CAS  Google Scholar 

  20. Huang J, Zhang J, Li H, et al. VCAM1 expression correlated with tumorigenesis and poor prognosis in high grade serous ovarian cancer. Am J Transl Res. 2013;5:336–46.

    PubMed  CAS  Google Scholar 

  21. Mao Y, Zhang DW, Lin H, et al. Alpha B-crystallin is a new prognostic marker for laryngeal squamous cell carcinoma. J Exp Clin Cancer Res. 2012;31:101.

    Article  PubMed  CAS  Google Scholar 

  22. Karanikas M, Machairiotis N, Zarogoulidis P, et al. Non-Hodgkin lymphoma and GIST: molecular pathways and clinical expressions. Onco Targets Ther. 2012;5:433–8.

    PubMed  Google Scholar 

  23. Tan CB, Zhi W, Shahzad G, et al. Gastrointestinal stromal tumors: a review of case reports, diagnosis, treatment, and future directions. ISRN Gastroenterol. 2012;2012:595968.

    PubMed  Google Scholar 

  24. Andtbacka RH, Ng CS, Scaife CL, et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol. 2007;14:14–24.

    Article  PubMed  Google Scholar 

  25. Hwang I, An BS, Yang H, et al. Tissue-specific expression of occludin, zona occludens-1, and junction adhesion molecule A in the duodenum, ileum, colon, kidney, liver, lung, brain, and skeletal muscle of C57BL mice. J Physiol Pharmacol. 2013;64:11–8.

    PubMed  CAS  Google Scholar 

  26. Gonzalez-Mariscal L, Lechuga S, Garay E. Role of tight junctions in cell proliferation and cancer. Prog Histochem Cytochem. 2007;42:1–57.

    Article  PubMed  CAS  Google Scholar 

  27. Martin TA, Jiang WG. Loss of tight junction barrier function and its role in cancer metastasis. Biochim Biophys Acta. 2009;1788:872–91.

    Article  PubMed  CAS  Google Scholar 

  28. Tsukita S, Yamazaki Y, Katsuno T, et al. Tight junction-based epithelial microenvironment and cell proliferation. Oncogene. 2008;27:6930–8.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This research was supported in part by grants from the Social Development and Applied Research Projects (K2010048 and K2010054), Nantong, China.

Conflict of interest

The authors declared that they have no competing interests.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Nantong University Affiliated Hospital, Nantong, China

    Huijun Zhu, Juying Lu & Xudong Wang

  2. Department of Gynecology and Obstetrics, Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Nanjing, China

    Huilin Zhang

  3. The Key Laboratory of Cancer Biomarkers, Prevention and Treatment Cancer Center and The Key Laboratory of Antibody Technique of the Ministry of Health, Nanjing Medical University, Nanjing, China

    Xiaojun Tang

  4. Huadong Medical Institute of Biotechnology, Nanjing, China

    Jin Zhu

  5. Department of Otolaryngology-Head and Neck Surgery, Jiangsu Provincial Hospital, Nanjing, China

    Yuan Mao

Authors
  1. Huijun Zhu
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  2. Juying Lu
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  3. Xudong Wang
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  4. Huilin Zhang
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  5. Xiaojun Tang
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  6. Jin Zhu
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  7. Yuan Mao
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Correspondence to Jin Zhu or Yuan Mao.

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Zhu, H., Lu, J., Wang, X. et al. Upregulated ZO-1 correlates with favorable survival of gastrointestinal stromal tumor. Med Oncol 30, 631 (2013). https://doi.org/10.1007/s12032-013-0631-7

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  • DOI: https://doi.org/10.1007/s12032-013-0631-7

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