Skip to main content

Advertisement

SpringerLink
Log in

The expression of SALL4 in patients with gliomas: high level of SALL4 expression is correlated with poor outcome

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The spalt-like transcription factor 4 (SALL4) gene has been demonstrated to be overexpressed in many malignancies, but little is known about its expression in gliomas. To explore the expression of SALL4 in patients with gliomas and the relationship between SALL4 expression and clinicopathologic characteristics, qPCR and immunohistochemical staining were used to investigate the SALL4 expression level in 54 glioma specimens and seven normal brain tissues. In vitro, siRNAs against SALL4 in U251 cell line were constructed and cell proliferation was evaluated by CCK8 assay. The SALL4 expression level in glioma was significantly higher than that in normal brain tissues (P < 0.05). Both qPCR and immunohistochemical analysis found that the expression of SALL4 was tightly correlated with glioma pathology grade (P < 0.05). Analysis using glioma and normal brain tissues revealed that SALL4 was positively proportionated to glioma cell differentiation with high sensitivity (92.59 %) and specificity (85.71 %). Survival analysis indicated the SALL4 expression was an independent prognostic factor. High level of SALL4 expression was correlated with poor outcome in patients with gliomas. This result agreed with the negative correlation between SALL4 expression and overall survival period obtaining in GBM patients from the cancer genome atlas database. The CCK8 experiments demonstrated SALL4 could significantly inhibit cell proliferation in U251 cell line (P < 0.05). The findings of the current study indicated that the SALL4 may play an important role in progression, development and maintenance of glioma.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Louis D, Ohgaki H, Wiestler O, Cavenee W, Burger P, Jouvet A, Scheithauer B, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed Central  PubMed  Google Scholar 

  2. Van Meir E, Hadjipanayis C, Norden A, Shu H, Wen P, Olson J (2010) Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 60:166–193

    Article  PubMed Central  PubMed  Google Scholar 

  3. Stupp R, Hegi M, Mason W, van den Bent M, Taphoorn M, Janzer R, Ludwin S, Allgeier A, Fisher B, Belanger K, Hau P, Brandes A, Gijtenbeek J, Marosi C, Vecht C, Mokhtari K, Wesseling P, Villa S, E E, G T, W M, L D, JG C, RO M, EOfRaToCBTaRO Groups, Group. NCIoCCT (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC–NCIC trial. Lancet Oncol 10:459–466

    Article  CAS  PubMed  Google Scholar 

  4. Mohyeldin A, Chiocca E (2012) Gene and viral therapy for glioblastoma: a review of clinical trials and future directions. Cancer J 18:82–88

    Article  CAS  PubMed  Google Scholar 

  5. Nicholas M, Lukas R, Jafri N, Faoro L, Salgia R (2006) Epidermal growth factor receptor—mediated signal transduction in the development and therapy of gliomas. Clin Cancer Res 12:7261–7270

    Article  CAS  PubMed  Google Scholar 

  6. Hägerstrand D, He X, Bradic Lindh M, Hoefs S, Hesselager G, Ostman A, Nistér M (2011) Identification of a SOX2-dependent subset of tumor- and sphere-forming glioblastoma cells with a distinct tyrosine kinase inhibitor sensitivity profile. Neuro Oncol 13:1178–1191

    Article  PubMed Central  PubMed  Google Scholar 

  7. Kohlhase J, Schuh R, Dowe G, Kühnlein R, Jäckle H, Schroeder B, Schulz-Schaeffer W, Kretzschmar H, Köhler A, Müller U, Raab-Vetter M, Burkhardt E, Engel W, Stick R (1996) Isolation, characterization, and organ-specific expression of two novel human zinc finger genes related to the drosophila gene spalt. Genomics 38:291–298

    Article  CAS  PubMed  Google Scholar 

  8. Zhang J, Tam W, Tong G, Wu Q, Chan H, Soh B, Lou Y, Yang J, Ma Y, Chai L, Ng H, Lufkin T, Robson P, Lim B (2006) Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol 8:1114–1123

    Article  CAS  PubMed  Google Scholar 

  9. Yang J, Gao C, Chai L, Ma Y (2010) A novel SALL4/OCT4 transcriptional feedback network for pluripotency of embryonic stem cells. PLoS One 5:e10766

    Article  PubMed Central  PubMed  Google Scholar 

  10. Cao D, Humphrey P, Allan R (2009) SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors. Cancer J 115:2640–2651

    Article  CAS  Google Scholar 

  11. Cao D, Li J, Guo C, Allan R, Humphrey P (2009) SALL4 is a novel diagnostic marker for testicular germ cell tumors. Am J Surg Pathol 33:1065–1077

    Article  PubMed  Google Scholar 

  12. Liu A, Cheng L, Du J, Peng Y, Allan R, Wei L, Li J, Cao D (2010) Diagnostic utility of novel stem cell markers SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in primary mediastinal germ cell tumors. Am J Surg Pathol 34:697–706

    PubMed  Google Scholar 

  13. Wang F, Liu A, Peng Y, Rakheja D, Wei L, Xue D, Allan R, Molberg K, Li J, Cao D (2009) Diagnostic utility of SALL4 in extragonadal yolk sac tumors: an immunohistochemical study of 59 cases with comparison to placentallike alkaline phosphatase, alpha-fetoprotein, and glypican-3. Am J Surg Pathol 33:1529–1539

    Article  PubMed  Google Scholar 

  14. Oikawa T, Kamiya A, Zeniya M, Chikada H, Hyuck A, Yamazaki Y, Wauthier E, Tajiri H, Miller L, Wang X, Reid L, Nakauchi H (2013) Sal-like protein 4 (SALL4), a stem cell biomarker in liver cancers. Hepatology 57:1469–1483

    Article  CAS  PubMed  Google Scholar 

  15. Kobayashi D, Kuribayashi K, Tanaka M, Watanabe N (2011) Overexpression of SALL4 in lung cancer and its importance in cell proliferation. Oncol Rep 26:965–970

    CAS  PubMed  Google Scholar 

  16. Kobayashi D, Kuribayshi K, Tanaka M, Watanabe N (2011) SALL4 is essential for cancer cell proliferation and is overexpressed at early clinical stages in breast cancer. Int J Oncol 38:933–939

    CAS  PubMed  Google Scholar 

  17. Yong K, Gao C, Lim J, Yan B, Yang H, Dimitrov T, Kawasaki A, Ong C, Wong K, Lee S, Ravikumar S, Srivastava S, Tian X, Poon R, Fan S, Luk J, Dan Y, Salto-Tellez M, Chai L, Tenen D (2013) Oncofetal gene SALL4 in aggressive hepatocellular carcinoma. N Engl J Med 13:2266–2276

    Article  Google Scholar 

  18. Aguila J, Liao W, Yang J, Avila C, Hagag N, Senzel L, Ma Y (2011) SALL4 is a robust stimulator for the expansion of hematopoietic stem cells. Blood 118:576–585

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Yang J, Aguila J, Alipio Z, Lai R, Fink L, Ma Y (2011) Enhanced self-renewal of hematopoietic stem/progenitor cells mediated by the stem cell gene Sall4. J Hematol Oncol 4:38

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Rao S, Zhen S, Roumiantsev S, McDonald L, Yuan G, Orkin S (2010) Differential roles of Sall4 isoforms in embryonic stem cell pluripotency. Mol Cell Biol 30:5364–5380

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Yang J, Chai L, Fowles T, Alipio Z, Xu D, Fink L, Ward D, Ma Y (2008) Genome–wide analysis reveals Sall4 to be a major regulator of pluripotency in murine–embryonic stem cells. Proc Natl Acad Sci U S A 105:19756–19761

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Yang J, Chai L, Fowles T, Alipio Z, Xu D, Fink L, Ward D, Ma Y (2008) Genome-wide analysis reveals Sall4 to be a major regulator of pluripotency in murine-embryonic stem cells. Proc Natl Acad Sci U S A 105:19756–19761

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Lim C, Tam W, Zhang J, Ang H, Jia H, Lipovich L, Ng H, Wei Sung W, Robson P, Yang H, Lim B (2008) Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages. Cell Stem Cell 3:543–554

    Article  CAS  PubMed  Google Scholar 

  24. Guo Y, Liu S, Wang P, Zhao S, Wang F, Bing L, Zhang Y, Ling E, Gao J, Hao A (2011) Expression of embryonic stem cell-associated genes Oct4, Sox2 and Nanog in human gliomas. Histopathology 59:763–775

    Article  PubMed  Google Scholar 

  25. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  PubMed  Google Scholar 

  26. Du Z, Jia D, Liu S, Wang F, Li G, Zhang Y, Cao X, Ling E, Hao A (2009) Oct4 is expressed in human gliomas and promotes colony formation in glioma cells. Glia 57:724–733

    Article  PubMed  Google Scholar 

  27. Annovazzi L, Mellai M, Caldera V, Valente G, Schiffer D (2011) SOX2 expression and amplification in gliomas and glioma cell lines. Cancer Genomics Proteomics 8:139–147

    CAS  PubMed  Google Scholar 

  28. Forghanifard M, Moghbeli M, Raeisossadati R, Tavassoli A, Mallak A, Boroumand-Noughabi S, Abbaszadegan M (2013) Role of SALL4 in the progression and metastasis of colorectal cancer. J Biomed Sci 20:6

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. He J, Zhang W, Zhou Q, Zhao T, Song Y, Chai L, Li Y (2013) Low-expression of microRNA-107 inhibits cell apoptosis in glioma by upregulation of SALL4. Int J Biochem Cell Biol 45:1962–1973

    Article  CAS  PubMed  Google Scholar 

  30. Wang F, Guo Y, Chen Q, Yang Z, Ning N, Zhang Y, Xu Y, Xu X, Tong C, Chai L, Cui W (2013) Stem cell factor SALL4, a potential prognostic marker for myelodysplastic syndromes. J Hematol Oncol 6:73

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work is supported by the National Natural Science Foundation of China (Grant Nos: 30930094; 81101908; 81001118).

Conflict of interest

We declared that there is no conflict of interest in this article.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Fengyang road, No. 415, Shanghai, 200003, China

    Lei Zhang, Yong Yan, Ying Jiang, Yong Cui, Yongxiang Zou, Jun Qian, Chun Luo, Yicheng Lu & Xiaojun Wu

Authors
  1. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yongxiang Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chun Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yicheng Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaojun Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yicheng Lu or Xiaojun Wu.

Additional information

Lei Zhang and Yong Yan have contributed equally to this study.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, L., Yan, Y., Jiang, Y. et al. The expression of SALL4 in patients with gliomas: high level of SALL4 expression is correlated with poor outcome. J Neurooncol 121, 261–268 (2015). https://doi.org/10.1007/s11060-014-1646-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-014-1646-4

Keywords

Search

Navigation