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Journal of Neuro-Oncology

, Volume 88, Issue 3, pp 281–291 | Cite as

Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR

  • Carlos A. Scrideli
  • Carlos G. CarlottiJr.
  • Oswaldo K. Okamoto
  • Vanessa S. Andrade
  • Maria A. A. Cortez
  • Fábio J. N. Motta
  • Agda K. Lucio-Eterovic
  • Luciano Neder
  • Sérgio Rosemberg
  • Sueli M. Oba-Shinjo
  • Suely K. N. Marie
  • Luíz G. Tone
Lab. investigation-human/animal tissue

Abstract

The prognosis of glioblastomas is still extremely poor and the discovery of novel molecular therapeutic targets can be important to optimize treatment strategies. Gene expression analyses comparing normal and neoplastic tissues have been used to identify genes associated with tumorigenesis and potential therapeutic targets. We have used this approach to identify differentially expressed genes between primary glioblastomas and non-neoplastic brain tissues. We selected 20 overexpressed genes related to cell cycle, cellular movement and growth, proliferation and cell-to-cell signaling and analyzed their expression levels by real time quantitative PCR in cDNA obtained from microdissected fresh tumor tissue from 20 patients with primary glioblastomas and from 10 samples of non-neoplastic white matter tissue. The gene expression levels were significantly higher in glioblastomas than in non-neoplastic white matter in 18 out of 20 genes analyzed: P < 0.00001 for CDKN2C, CKS2, EEF1A1, EMP3, PDPN, BNIP2, CA12, CD34, CDC42EP4, PPIE, SNAI2, GDF15 and MMP23b; and NFIA (P: 0.0001), GPS1 (P: 0.0003), LAMA1 (P: 0.002), STIM1 (P: 0.006), and TASP1 (P: 0.01). Five of these genes are located in contiguous loci at 1p31–36 and 2 at 17q24–25 and 8 of them encode surface membrane proteins. PDPN and CD34 protein expression were evaluated by immunohistochemistry and they showed concordance with the PCR results. The present results indicate the presence of 18 overexpressed genes in human primary glioblastomas that may play a significant role in the pathogenesis of these tumors and that deserve further functional investigation as attractive candidates for new therapeutic targets.

Keywords

Glioblastoma Brain Gene expression Microarray RQ-PCR 

Notes

Acknowledgments

We thank Rosane P. Queiroz, Sandra L. B. P. Martins and Miyuki Uno for technical assistance and Dr. Paulo Henrique Aguiar for neurosurgical assistance in sample collection. This work was supported by the Brazilian Governmental agencies FAPESP (Grant No. 04/1233-6) and FAEPA.

Supplementary material

11060_2008_9579_MOESM1_ESM.xls (108 kb)
The complete list of the 562 genes showing at least 2-fold increase in expression in glioblastomas as compared to non neoplastic brain and grouped according to GO criteria. (PDF 108 KB)

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Carlos A. Scrideli
    • 1
    • 2
  • Carlos G. CarlottiJr.
    • 3
  • Oswaldo K. Okamoto
    • 4
  • Vanessa S. Andrade
    • 5
  • Maria A. A. Cortez
    • 5
  • Fábio J. N. Motta
    • 5
  • Agda K. Lucio-Eterovic
    • 1
  • Luciano Neder
    • 6
  • Sérgio Rosemberg
    • 7
  • Sueli M. Oba-Shinjo
    • 8
  • Suely K. N. Marie
    • 8
  • Luíz G. Tone
    • 1
  1. 1.Department of Pediatrics, Faculty of Medicine of Ribeirão PretoUniversity of São PauloRibeirao PretoBrazil
  2. 2.Departamento de Puericultura e PediatriaUniversity of São PauloRibeirão PretoBrazil
  3. 3.Department of Surgery, Faculty of Medicine of Ribeirão PretoUniversity of São PauloRibeirão PretoBrazil
  4. 4.Department of Neurology and NeurosurgeryFederal University of São PauloSão PauloBrazil
  5. 5.Department of Genetics, Faculty of Medicine of Ribeirão PretoUniversity of São PauloRibeirao PretoBrazil
  6. 6.Department of Pathology, Faculty of Medicine of Ribeirão PretoUniversity of São PauloRibeirao PretoBrazil
  7. 7.Department of Pathology, Faculty of MedicineUniversity of São PauloSão PauloBrazil
  8. 8.Department of Neurology, Faculty of MedicineUniversity of São PauloSão PauloBrazil

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