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Tumor Biology

, Volume 36, Issue 11, pp 8333–8340 | Cite as

SEMA6A is a prognostic biomarker in glioblastoma

  • Jiaxin Zhao
  • Haitao Tang
  • Hong Zhao
  • Wanli Che
  • Lei Zhang
  • Peng Liang
Research Article

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.

Keywords

SEMA6A Glioblastoma multiforme (GBM) Prognosis Proliferation Invasion 

Notes

Acknowledgments

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

Conflicts of interest

None.

References

  1. 1.
    Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;359:492–507.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Semaphorin Nomenclature Committee. Letter to the editor: unified nomenclature for the semaphorins/collapsins. Cell. 1999;97:551–2.CrossRefGoogle Scholar
  5. 5.
    Pasterkamp RJ. Getting neural circuits into shape with semaphorins. Nat Rev Neurosci. 2012;13:605–18.CrossRefPubMedGoogle Scholar
  6. 6.
    Gu C, Giraudo E. The role of semaphorins and their receptors in vascular development and cancer. Exp Cell Res. 2013;319:1306–16.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Kumanogoh A, Kikutani H. Immunological functions of the neuropilins and plexins as receptors for semaphorins. Nat Rev Immunol. 2013;13:802–14.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 25.
    Segarra M, Ohnuki H, Maric D, et al. Semaphorin 6A regulates angiogenesis by modulating VEGF signaling. Blood. 2012;120:4104–15.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Schlaepfer DD, Hauck CR, Sieg DJ. Signaling through focal adhesion kinase. Prog Biophys Mol Biol. 1999;71:435–78.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 29.
    Natarajan M, Hecker TP, Gladson CL. FAK signaling in anaplastic astrocytoma and glioblastoma tumors. Cancer J. 2003;9:126–33.CrossRefPubMedGoogle Scholar
  30. 30.
    Potiron VA, Roche J, Drabkin HA. Semaphorins and their receptors in lung cancer. Cancer Lett. 2009;273:1–14.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jiaxin Zhao
    • 1
  • Haitao Tang
    • 2
  • Hong Zhao
    • 3
  • Wanli Che
    • 4
  • Lei Zhang
    • 4
  • Peng Liang
    • 4
  1. 1.Department of NeurosurgeryThe Fourth Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Department of NeurosurgeryThe General Hospital of Daqing Oil FieldDaqingChina
  3. 3.Department of Medical OncologyThe Third Affiliated Hospital of Harbin Medical UniversityHarbinChina
  4. 4.Department of NeurosurgeryThe Third Affiliated Hospital of Harbin Medical UniversityHarbinChina

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