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Expression of EphrinB2 and EphB4 in glioma tissues correlated to the progression of glioma and the prognosis of glioblastoma patients

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Abstract

Objective

The ligand EphrinB2 and the corresponding receptor EphB4 are up-regulated and involved in tumour growth in various human cancers. However, little is known about how this receptor-ligand complex contributes to the progression of glioma. This prompted us to study the association between the expressions of EphrinB2 and EphB4, clinicopathological variables, and glioma patient outcome.

Methods

Immunohistochemical staining was performed to detect the expression patterns of EphrinB2 and EphB4 in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients.

Results

Immunohistochemical analysis revealed that the expression of EphrinB2 was significantly correlated with that of EphB4 (r=0.86, p=0.002). EphrinB2 and EphB4 were significantly associated with the Karnofsky performance scale (KPS) score and World Health Organization grades of patients with gliomas, respectively. Especially, the positive expression rates of EphrinB2 and EphB4 were significantly higher in patients with higher grade (both p=0.001) and lower KPS score (p=0.002 and 0.003, respectively). Multivariate Cox regression analysis revealed that EphrinB2 and EphB4 expressions were both independent prognostic factors for progress-free survival of glioblastoma patients (both p=0.02).

Conclusion

Our data indicated for the first time that EphrinB2 and EphB4 expressions increase according to the histopathological grade and KPS score of glioma, and their expression levels are related to the progression-free survival of glioblastoma patients.

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References

  1. Rainov NG, Heidecke V (2011) Clinical development of experimental therapies for malignant glioma. Sultan Qaboos Univ Med J 11:5–28

    PubMed  Google Scholar 

  2. Kleihues P, Sobin LH (2000) World Health Organization classification of tumors. Cancer 88:2887

    Article  PubMed  CAS  Google Scholar 

  3. Pasquale EB (1997) The Eph family of receptors. Curr Opin Cell Biol 9:608–615

    Article  PubMed  CAS  Google Scholar 

  4. Maekawa H, Oike Y, Kanda S et al (2003) EphrinB2 induces migration of endothelial cells through the phosphatidylinositol-3 kinase pathway and promotes angiogenesis in adult vasculature. Arterioscler Thromb Vasc Biol 23:2008–2014

    Article  PubMed  CAS  Google Scholar 

  5. Das A, Shergill U, Thakur L et al (2010) Ephrin B2/EphB4 pathway in hepatic stellate cells stimulates Erk-dependent VEGF production and sinusoidal endothelial cell recruitment. Am J Physiol Gastrointest Liver Physiol 298:G908–G915

    Article  PubMed  CAS  Google Scholar 

  6. Xia G, Kumar SR, Masood R et al (2005) EphB4 expression and biological significance in prostate cancer. Cancer Res 65:4623–4632

    Article  PubMed  CAS  Google Scholar 

  7. Noren NK, Lu M, Freeman AL et al (2004) Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth. Proc Natl Acad Sci USA 101:5583–5588

    Article  PubMed  CAS  Google Scholar 

  8. Kullander K, Klein R (2002) Mechanisms and functions of Eph and ephrin signaling. Nat Rev Mol Cell Biol 3:475–486

    Article  PubMed  CAS  Google Scholar 

  9. Fox BP, Kandpal RP (2004) Invasiveness of breast carcinoma cells and transcript profile: Eph receptors and ephrin ligands as molecular markers of potential diagnostic and prognostic application. Biochem Biophys Res Commun 318:882–892

    Article  PubMed  CAS  Google Scholar 

  10. Tang XX, Brodeur GM, Campling BG et al (1999) Coexpression of transcripts encoding EPHB receptor protein tyrosine kinases and their ephrin-B ligands in human small cell lung carcinoma. Clin Cancer Res 5:455–460

    PubMed  CAS  Google Scholar 

  11. Tang XX, Jhao H, Robinson ME et al (2000) Implication of EPHB6, EFNB2 and EFNB3 expression in human neuroblastoma. Proc Natl Acad Sci U S A 97:10936–10941

    Article  PubMed  CAS  Google Scholar 

  12. Martiny-Baron G, Holzer P, Billy E et al (2010) The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis. Angiogenesis 13: 259–267

    Article  PubMed  CAS  Google Scholar 

  13. Branco-Price C, Johnson RS (2010) Tumor vessels are Eph-ing complicated. Cancer Cell 17:533–534

    Article  PubMed  CAS  Google Scholar 

  14. Kumar SR, Scehnet JS, Ley EJ et al (2009) Preferential induction of EphB4 over EphB2 and its implication in colorectal cancer progression. Cancer Res 69:3736–3745

    Article  PubMed  CAS  Google Scholar 

  15. Pennisi A, Ling W, Li X et al (2009) The ephrinB2/ EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth. Blood 114:1803–1812

    Article  PubMed  CAS  Google Scholar 

  16. Héroult M, Schaffner F, Pfaff D et al (2010) EphB4 promotes site-specific metastatic tumor cell dissemination by interacting with endothelial cellexpressed ephrinb2. Mol Cancer Res 8:1297–1309

    Article  PubMed  Google Scholar 

  17. Xue C, Huang Z, Wang J et al (2009) EphrinB2 and EphB4 expression in pterygia: new insights and preliminary results. Can J Ophthalmol 44:185–188

    Article  PubMed  Google Scholar 

  18. Yamanda S, Ebihara S, Asada M et al (2009) Role of ephrinB2 in nonproductive angiogenesis induced by Delta-like 4 blockade. Blood 113:3631–3639

    Article  PubMed  CAS  Google Scholar 

  19. Alam SM, Fujimoto J, Jahan I et al (2007) Overexpression of ephrinB2 and EphB4 in tumor advancement of uterine endometrial cancers. Ann Oncol 18:485–490

    Article  PubMed  CAS  Google Scholar 

  20. Alam SM, Fujimoto J, Jahan I et al (2009) Coexpression of EphB4 and ephrinB2 in tumor advancement of uterine cervical cancers. Gynecol Oncol 114:84–88

    Article  PubMed  CAS  Google Scholar 

  21. McCarty KS Jr, Miller LS, Cox EB et al (1985) Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 109:716–721

    Google Scholar 

  22. Catt SL, Anderson JL, Critchley GR (2011) Patients’ and staff’s experiences of multidisciplinary follow-up for high-grade glioma after radical radiotherapy. Psychol Health Med 16:357–365

    Article  PubMed  Google Scholar 

  23. Walbert T, Mikkelsen T (2011) Recurrent highgrade glioma: a diagnostic and therapeutic challenge. Expert Rev Neurother 11:509–518

    Article  PubMed  Google Scholar 

  24. Batlle E, Bacani J, Begthel H et al (2005) Ephb receptor activity suppresses colorectal cancer progression. Nature 435:1126–1130

    Article  PubMed  CAS  Google Scholar 

  25. Wu D, Suo Z, Kristensen GB et al (2004) Prognostic value of epha2 and ephrina-1 in squamous cell cervical carcinoma. Gynecol Oncol 94:312–319

    Article  PubMed  CAS  Google Scholar 

  26. Wu Q, Suo Z, Risberg B et al (2004) Expression of ephb2 and ephb4 in breast carcinoma. Pathol Oncol Res 10:26–33

    Article  PubMed  CAS  Google Scholar 

  27. Xia G, Kumar SR, Stein JP et al (2006) EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival. Oncogene 25:769–780

    Article  PubMed  CAS  Google Scholar 

  28. Masood R, Kumar SR, Sinha UK et al (2006) EphB4 provides survival advantage to squamous cell carcinoma of the head and neck. Int J Cancer 119:1236–1248

    Article  PubMed  CAS  Google Scholar 

  29. Kumar SR, Singh J, Xia G et al (2006) Receptor tyrosine kinase EphB4 is a survival factor in breast cancer. Am J Pathol 169:279–293

    Article  PubMed  CAS  Google Scholar 

  30. Yavrouian EJ, Sinha UK, Rice DH et al (2008) The significance of EphB4 and EphrinB2 expression and survival in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 134:985–991

    Article  PubMed  Google Scholar 

  31. Ozgür E, Heidenreich A, Dagtekin O et al (2011) Distribution of EphB4 and EphrinB2 in normal and malignant urogenital tissue. Urol Oncol 29:78–84

    Article  PubMed  Google Scholar 

  32. Krasnoperov V, Kumar SR, Ley E et al (2010) Novel EphB4 monoclonal antibodies modulate angiogenesis and inhibit tumor growth. Am J Pathol 176:2029–2038

    Article  PubMed  CAS  Google Scholar 

  33. Erber R, Eichelsbacher U, Powajbo V et al (2006) EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. EMBO J 25:628–641

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Emergency, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China

    Yanyang Tu

  2. Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China

    Shiming He, Gang Li & Jianping Deng

  3. Department of Endocrine, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Jianfang Fu

  4. Department of Neurosurgery, General Hospital of Beijing Military Zone, Beijing, 100041, China

    Ruxiang Xu & Hongliu Lu

Authors
  1. Yanyang Tu
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  2. Shiming He
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  3. Jianfang Fu
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  4. Gang Li
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  5. Ruxiang Xu
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  6. Hongliu Lu
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  7. Jianping Deng
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Corresponding author

Correspondence to Jianping Deng.

Additional information

This work was funded by the National Natural Science Foundation of China (No. 81101736).

These three authors contributed equally to this work.

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Tu, Y., He, S., Fu, J. et al. Expression of EphrinB2 and EphB4 in glioma tissues correlated to the progression of glioma and the prognosis of glioblastoma patients. Clin Transl Oncol 14, 214–220 (2012). https://doi.org/10.1007/s12094-012-0786-2

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  • DOI: https://doi.org/10.1007/s12094-012-0786-2

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