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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

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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.

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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.

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirao Preto, SP, Brazil

    Carlos A. Scrideli, Agda K. Lucio-Eterovic & Luíz G. Tone

  2. Departamento de Puericultura e Pediatria, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brazil

    Carlos A. Scrideli

  3. Department of Surgery, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil

    Carlos G. Carlotti Jr.

  4. Department of Neurology and Neurosurgery, Federal University of São Paulo, 04023-900, São Paulo, SP, Brazil

    Oswaldo K. Okamoto

  5. Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirao Preto, SP, Brazil

    Vanessa S. Andrade, Maria A. A. Cortez & Fábio J. N. Motta

  6. Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirao Preto, SP, Brazil

    Luciano Neder

  7. Department of Pathology, Faculty of Medicine, University of São Paulo, 01246-903, São Paulo, SP, Brazil

    Sérgio Rosemberg

  8. Department of Neurology, Faculty of Medicine, University of São Paulo, 01246-903, São Paulo, SP, Brazil

    Sueli M. Oba-Shinjo & Suely K. N. Marie

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  1. Carlos A. Scrideli
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Correspondence to Carlos A. Scrideli.

Electronic Supplementary Material

11060_2008_9579_MOESM1_ESM.xls

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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Scrideli, C.A., Carlotti, C.G., Okamoto, O.K. et al. 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. J Neurooncol 88, 281–291 (2008). https://doi.org/10.1007/s11060-008-9579-4

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