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SEMA6A is a prognostic biomarker in glioblastoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Glioblastoma multiforme (GBM) is one of the most aggressive tumors in the central nervous system. SEMA6A, the first identified class 6 semaphorin, is contributed to regulate vascular development and adult angiogenesis. However, the function of SEMA6A in GBM is still undefined. In the present study, we investigated the expression of SEMA6A protein in 200 GBM tissues using immunohistochemistry (IHC). SEMA6A expression was associated with time to progression (P = 0.001) and mean tumor diameter (P = 0.038). Kaplan–Meier analysis revealed that patients expressing high SEMA6A protein levels had a significantly longer overall survival (OS, P = 0.013) and progression-free survival (PFS, P = 0.005) compared to those with low SEMA6A expression level. Cox multivariate regression analysis confirmed that low SEMA6A expression was an independent unfavorable prognostic factors for PFS (HR, 1.896; 95 % CI, 1.147–2.768; P = 0.009) and OS (HR, 1.712; 95 % CI, 1.011–2.657; P = 0.012). Furthermore, in vitro experiments showed that SEMA6A could inhibit proliferation, migration, and invasion in different glioma cell lines. In conclusion, our findings indicated that SEMA6A may be a potential prognostic biomarker in the treatment of GBM.

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References

  1. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;359:492–507.

    Article  CAS  PubMed  Google Scholar 

  2. Rousseau A, Mokhtari K, Duyckaerts C. The 2007 WHO classification of tumors of the central nervous system—what has changed? Curr Opin Neurol. 2008;21:720–7.

    Article  PubMed  Google Scholar 

  3. Van Meir EG, Hadjipanayis CG, Norden AD, et al. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin. 2010;60:166–93.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Semaphorin Nomenclature Committee. Letter to the editor: unified nomenclature for the semaphorins/collapsins. Cell. 1999;97:551–2.

    Article  Google Scholar 

  5. Pasterkamp RJ. Getting neural circuits into shape with semaphorins. Nat Rev Neurosci. 2012;13:605–18.

    Article  CAS  PubMed  Google Scholar 

  6. Gu C, Giraudo E. The role of semaphorins and their receptors in vascular development and cancer. Exp Cell Res. 2013;319:1306–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kumanogoh A, Kikutani H. Immunological functions of the neuropilins and plexins as receptors for semaphorins. Nat Rev Immunol. 2013;13:802–14.

    Article  PubMed  Google Scholar 

  8. Martin-Satue M, Blanco J. Identification of semaphorin E gene expression in metastatic human lung adenocarcinoma cells by mRNA differential display. J Surg Oncol. 1999;72:18–23.

    Article  CAS  PubMed  Google Scholar 

  9. Deaglio S, Vaisitti T, Bergui L, et al. CD38 and CD100 lead a network of surface receptors relaying positive signals for B‑CLL growth and survival. Blood. 2005;105:3042–50.

    Article  CAS  PubMed  Google Scholar 

  10. Hu B, Guo P, Bar-Joseph I, et al. Neuropilin‑1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway. Oncogene. 2007;26:5577–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hirota E, Yan L, Tsunoda T, et al. Genome-wide gene expression profiles of clear cell renal cell carcinoma: Identification of molecular targets for treatment of renal cell carcinoma. Int J Oncol. 2006;29:799–827.

    CAS  PubMed  Google Scholar 

  12. Zhou L, White FA, Lentz SI, et al. Cloning and expression of a novel murine semaphorin with structural similarity to insect semaphorin I. Mol Cell Neurosci. 1997;9:26–41.

    Article  CAS  PubMed  Google Scholar 

  13. Bron R, Vermeren M, Kokot N, et al. Boundary cap cells constrain spinal motor neuron somal migration at motor exit points by a semaphorin–plexin mechanism. Neural Dev. 2007;2:21.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Little GE, López-Bendito G, Rünker AE, et al. Specificity and plasticity of thalamocortical connections in Sema6A mutant mice. PLoS Biol. 2009;7, e98.

    Article  PubMed  Google Scholar 

  15. Mauti O, Domanitskaya E, Andermatt I, et al. Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system. Neural Dev. 2007;2:28.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rünker AE, Little GE, Suto F, et al. Semaphorin-6A controls guidance of corticospinal tract axons at multiple choice points. Neural Dev. 2008;3:34.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Suto F, Tsuboi M, Kamiya H, et al. Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers. Neuron. 2007;53:535–47.

    Article  CAS  PubMed  Google Scholar 

  18. Bernard F, Moreau-Fauvarque C, Heitz-Marchaland C, et al. Role of transmembrane semaphoring Sema6A in oligodendrocyte differentiation and myelination. Glia. 2012;60(1):590–1604.

    Google Scholar 

  19. Loria R, Bon G, Perotti V, et al. Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells. Oncotarget. 2015;6(5):2779–93.

    Article  PubMed  Google Scholar 

  20. Dhanabal M, Wu F, Alvarez E, et al. Recombinant semaphorin 6A‑1ectodomain inhibits in vivo growth factor and tumor cell line-induced angiogenesis. Cancer Biol Ther. 2005;4:659–68.

    Article  CAS  PubMed  Google Scholar 

  21. Tran-Van H, Avota E, Börtlein C, et al. Measles virus modulates dendritic cell/T-cell communication at the level of plexinA1/neuropilin-1 recruitment and activity. Eur J Immunol. 2011;41:151–63.

    Article  CAS  PubMed  Google Scholar 

  22. Ueno K, Kumagai T, Kijima T, et al. Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer. Hum Genet. 1998;102:63–8.

    Article  CAS  PubMed  Google Scholar 

  23. Prislei S, Mozzetti S, Filippetti F, et al. From plasma membrane to cytoskeleton: a novel function for semaphorin 6A. Mol Cancer Ther. 2008;7(1):233–41.

    Article  CAS  PubMed  Google Scholar 

  24. Urbich C, Kaluza D, Frömel T, et al. MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. Blood. 2012;119:1607–16.

    Article  CAS  PubMed  Google Scholar 

  25. Segarra M, Ohnuki H, Maric D, et al. Semaphorin 6A regulates angiogenesis by modulating VEGF signaling. Blood. 2012;120:4104–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Schlaepfer DD, Hauck CR, Sieg DJ. Signaling through focal adhesion kinase. Prog Biophys Mol Biol. 1999;71:435–78.

    Article  CAS  PubMed  Google Scholar 

  27. Parsons JT, Martin KH, Slack JK, et al. Focal adhesion kinase: a regulator of focal adhesion dynamics and cell movement. Oncogene. 2000;19:5606–13.

    Article  CAS  PubMed  Google Scholar 

  28. Rutka JT, Muller M, Hubbard SL, et al. Astrocytoma adhesion to extracellular matrix: functional significance of integrin and focal adhesion kinase expression. J Neuropathol Exp Neurol. 1999;58:198–209.

    Article  CAS  PubMed  Google Scholar 

  29. Natarajan M, Hecker TP, Gladson CL. FAK signaling in anaplastic astrocytoma and glioblastoma tumors. Cancer J. 2003;9:126–33.

    Article  CAS  PubMed  Google Scholar 

  30. Potiron VA, Roche J, Drabkin HA. Semaphorins and their receptors in lung cancer. Cancer Lett. 2009;273:1–14.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Health and Family Planning Commission of Heilongjiang Province [grant number 2014-403].

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin Yiyuan Road No. 37 of Nangang District, Harbin, 150001, Heilongjiang, China

    Jiaxin Zhao

  2. Department of Neurosurgery, The General Hospital of Daqing Oil Field, Zhongkang Road 9 of Saertu District, Daqing, 163001, Heilongjiang, China

    Haitao Tang

  3. Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road No. 150 of Nangang District, Harbin, 150081, Heilongjiang, China

    Hong Zhao

  4. Department of Neurosurgery, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, 150081, Heilongjiang, China

    Wanli Che, Lei Zhang & Peng Liang

Authors
  1. Jiaxin Zhao
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  2. Haitao Tang
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  3. Hong Zhao
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  4. Wanli Che
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  5. Lei Zhang
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  6. Peng Liang
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Corresponding author

Correspondence to Peng Liang.

Additional information

Jiaxin Zhao and Haitao Tang contributed equally to the work and should be considered co-first authors.

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Zhao, J., Tang, H., Zhao, H. et al. SEMA6A is a prognostic biomarker in glioblastoma. Tumor Biol. 36, 8333–8340 (2015). https://doi.org/10.1007/s13277-015-3584-y

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  • DOI: https://doi.org/10.1007/s13277-015-3584-y

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